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In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice

Abstract

The ability to modify mice genetically has been one of the major breakthroughs in modern medical science affecting every discipline including psychiatry. It is hoped that the application of such technologies will result in the identification of novel targets for the treatment of diseases such as depression and to gain a better understanding of the molecular pathophysiological mechanisms that are regulated by current clinically effective antidepressant medications. The advent of these tools has resulted in the need to adopt, refine and develop mouse-specific models for analyses of depression-like behavior or behavioral patterns modulated by antidepressants. In this review, we will focus on the utility of current models (eg forced swim test, tail suspension test, olfactory bulbectomy, learned helplessness, chronic mild stress, drug-withdrawal-induced anhedonia) and research strategies aimed at investigating novel targets relevant to depression in the mouse. We will focus on key questions that are considered relevant for examining the utility of such models. Further, we describe other avenues of research that may give clues as to whether indeed a genetically modified animal has alterations relevant to clinical depression. We suggest that it is prudent and most appropriate to use convergent tests that draw on different antidepressant-related endophenotypes, and complimentary physiological analyses in order to provide a program of information concerning whether a given phenotype is functionally relevant to depression-related pathology.

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References

  1. Wong ML, Licinio J . Research, treatment approaches to depression. Nat Rev Neurosci 2001; 2: 343–351.

    Article  CAS  PubMed  Google Scholar 

  2. Murray CJ, Lopez AD . Alternative projections of mortality and disability by cause mru1990–2020 Global Burden of Disease Study. Lancet 1997; 349: 1498–1504.

    Article  CAS  PubMed  Google Scholar 

  3. Kessler RC, Beglund P, Demler O, Jin R, Koretz D, Merikangas KR et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003; 289: 3095–3105.

    Article  PubMed  Google Scholar 

  4. Stewart WF, Ricci JA, Chee E, Hahn SR, Morganstein D . Cost of lost productive work time among US workers with depression. JAMA 2003; 289: 3135–3144.

    Article  PubMed  Google Scholar 

  5. Frazer A . Antidepressants. J Clin Psychiatry 1997; 58(Suppl 6): 9–25.

    CAS  PubMed  Google Scholar 

  6. Tecott LH . The genes and brains of mice and men. Am J Psychiatry 2003; 160: 646–656.

    Article  PubMed  Google Scholar 

  7. Cowan WM, Kopnisky KL, Hyman SE . The human genome project and its impact on psychiatry. Annu Rev Neurosci 2002; 25: 1–50.

    Article  CAS  PubMed  Google Scholar 

  8. Bucan M, Abel T . The mouse: genetics meets behaviour. Nat Rev Genet 2002; 3: 114–123.

    Article  CAS  PubMed  Google Scholar 

  9. Tecott LH, Wehner JM . Mouse molecular genetic technologies: promise for psychiatric research. Arch Gen Psychiatry 2001; 58: 995–1004.

    Article  CAS  PubMed  Google Scholar 

  10. Xu F, Gainetdinov RR, Wetsel WC, Jones SR, Bohn LM, Miller GW et al. Mice lacking the norepinephrine transporter are supersensitive to psychostimulants. Nat Neurosci 2000; 3: 465–471.

    Article  CAS  PubMed  Google Scholar 

  11. Cryan JF, Kelly PH, Neijt HC, Sansig G, Flor PJ, Van Der Putten H . Antidepressant and anxiolytic-like effects in mice lacking the group III metabotropic glutamate receptor mGluR7. Eur J Neurosci 2003; 17: 2409–2417.

    Article  PubMed  Google Scholar 

  12. Ramboz S, Oosting R, Amara DA, Kung HF, Blier P, Mendelsohn M et al. Serotonin receptor 1A knockout: an animal model of anxiety-related disorder. Proc Natl Acad Sci USA 1998; 95: 14476–14481.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Parks CL, Robinson PS, Sibille E, Shenk T, Toth M . Increased anxiety of mice lacking the serotonin1A receptor. Proc Natl Acad Sci USA 1998; 95: 10734–10739.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Heisler LK, Chu HM, Brennan TJ, Danao JA, Bajwa P, Parsons LH et al. Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice. Proc Natl Acad Sci USA 1998; 95: 15049–15054.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Mayorga AJ, Dalvi A, Page ME, Zimov-Levinson S, Hen R, Lucki I . Antidepressant-like behavioral effects in 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) receptor mutant mice. J Pharmacol Exp Ther 2001; 298: 1101–1107.

    CAS  PubMed  Google Scholar 

  16. Knobelman DA, Hen R, Blendy JA, Lucki I . Regional patterns of compensation following genetic deletion of either 5-hydroxytryptamine(1A) or 5-hydroxytryptamine(1B) receptor in the mouse. J Pharmacol Exp Ther 2001; 298: 1092–1100.

    CAS  PubMed  Google Scholar 

  17. Boutrel B, Monaca C, Hen R, Hamon M, Adrien J . Involvement of 5-HT1A receptors in homeostatic and stress-induced adaptive regulations of paradoxical sleep: studies in 5-HT1A knock-out mice. J Neurosci 2002; 22: 4686–4692.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Knobelman DA, Hen R, Lucki I . Genetic regulation of extracellular serotonin by 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) autoreceptors in different brain regions of the mouse. J Pharmacol Exp Ther 2001; 298: 1083–1091.

    CAS  PubMed  Google Scholar 

  19. De Groote L, Olivier B, Westenberg HG . The effects of selective serotonin reuptake inhibitors on extracellular 5-HT levels in the hippocampus of 5-HT(1B) receptor knockout mice. Eur J Pharmacol 2002; 439: 93–100.

    Article  CAS  PubMed  Google Scholar 

  20. Malagie I, David DJ, Jolliet P, Hen R, Bourin M, Gardier AM . Improved efficacy of fluoxetine in increasing hippocampal 5-hydroxytryptamine outflow in 5-HT(1B) receptor knock-out mice. Eur J Pharmacol 2002; 443: 99–104.

    Article  CAS  PubMed  Google Scholar 

  21. Holmes A, Yang RJ, Murphy DL, Crawley JN . Evaluation of antidepressant-related behavioral responses in mice lacking the serotonin transporter. Neuropsychopharmacology 2002; 27: 914–923.

    Article  CAS  PubMed  Google Scholar 

  22. Li Q, Wichems C, Heils A, Van De Kar LD, Lesch KP, Murphy DL . Reduction of 5-hydroxytryptamine (5-HT)(1A)-mediated temperature and neuroendocrine responses and 5-HT(1A) binding sites in 5-HT transporter knockout mice. J Pharmacol Exp Ther 1999; 291: 999–1007.

    CAS  PubMed  Google Scholar 

  23. Gobbi G, Murphy DL, Lesch K, Blier P . Modifications of the serotonergic system in mice lacking serotonin transporters: an in vivo electrophysiological study. J Pharmacol Exp Ther 2001; 296: 987–995.

    CAS  PubMed  Google Scholar 

  24. Mannoury la Cour C, Boni C, Hanoun N, Lesch KP, Hamon M, Lanfumey L . Functional consequences of 5-HT transporter gene disruption on 5-HT(1a) receptor-mediated regulation of dorsal raphe and hippocampal cell activity. J Neurosci 2001; 21: 2178–2185.

    Article  CAS  PubMed  Google Scholar 

  25. Guscott MR . The effect of 5-HT7 receptor knockout in mouse forced swim test. Abstract from Conference “Serotonin: From the Molecule to Clinic” 2000, p 81.

  26. Cryan JF, Dalvi A, Jin SH, Hirsch BR, Lucki I, Thomas SA . Use of dopamine-beta-hydroxylase-deficient mice to determine the role of norepinephrine in the mechanism of action of antidepressant drugs. J Pharmacol Exp Ther 2001; 298: 651–657.

    CAS  PubMed  Google Scholar 

  27. Schramm NL, McDonald MP, Limbird LE . The alpha(2a)-adrenergic receptor plays a protective role in mouse behavioral models of depression and anxiety. J Neurosci 2001; 21: 4875–4882.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sallinen J, Haapalinna A, MacDonald E, Viitamaa T, Lahdesmaki J, Rybnikova E et al. Genetic alteration of the alpha2-adrenoceptor subtype c in mice affects the development of behavioral despair and stress-induced increases in plasma corticosterone levels. Mol Psychiatry 1999; 4: 443–452.

    Article  CAS  PubMed  Google Scholar 

  29. Haller J, Bakos N, Rodriguiz RM, Caron MG, Wetsel WC, Liposits Z . Behavioral responses to social stress in noradrenaline transporter knockout mice: effects on social behavior and depression. Brain Res Bull 2002; 58: 279–284.

    Article  CAS  PubMed  Google Scholar 

  30. Cases O, Seif I, Grimsby J, Gaspar P, Chen K, Pournin S et al. Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA. Science 1995; 268: 1763–1766.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Evrard A, Malagie I, Laporte AM, Boni C, Hanoun N, Trillat AC et al. Altered regulation of the 5-HT system in the brain of MAO-A knock-out mice. Eur J Neurosci 2002; 15: 841–851.

    Article  CAS  PubMed  Google Scholar 

  32. Grimsby J, Toth M, Chen K, Kumazawa T, Klaidman L, Adams JD et al. Increased stress response and beta-phenylethylamine in MAOB-deficient mice. Nat Genet 1997; 17: 206–210.

    Article  CAS  PubMed  Google Scholar 

  33. Filliol D, Ghozland S, Chluba J, Martin M, Matthes HW, Simonin F et al. Mice deficient for delta- and mu-opioid receptors exhibit opposing alterations of emotional responses. Nat Genet 2000; 25: 195–200.

    Article  CAS  PubMed  Google Scholar 

  34. Stork O, Ji FY, Kaneko K, Stork S, Yoshinobu Y, Moriya T et al.Postnatal development of a GABA deficit and disturbance of neural functions in mice lacking GAD65. Brain Res 2000; 865: 45–58.

    Article  CAS  PubMed  Google Scholar 

  35. Mombereau C, Kaupmann K, Sansig S, van der Putten H, Cryan JF . GABAB receptors play a key role in the modulation of anxiety, depression-related behaviours. Behav Pharmacol 2003; 14(Suppl 1): 24.

    Google Scholar 

  36. Miyamoto Y, Yamada K, Noda Y, Mori H, Mishina M, Nabeshima T . Lower sensitivity to stress and altered monoaminergic neuronal function in mice lacking the NMDA receptor epsilon 4 subunit. J Neurosci 2002; 22: 2335–2342.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Rupniak NM, Carlson EJ, Webb JK, Harrison T, Porsolt RD, Roux S et al. Comparison of the phenotype of NK1R−/− mice with pharmacological blockade of the substance P (NK1) receptor in assays for antidepressant and anxiolytic drugs. Behav Pharmacol 2001; 12: 497–508.

    Article  CAS  PubMed  Google Scholar 

  38. Santarelli L, Gobbi G, Blier P, Hen R . Behavioral, physiologic effects of genetic or pharmacologic inactivation of the substance P receptor (NK1). J Clin Psychiatry 2002; 63(Suppl 11): 11–17.

    CAS  PubMed  Google Scholar 

  39. Froger N, Gardier AM, Moratalla R, Alberti I, Lena I, Boni C et al. 5-Hydroxytryptamine (5-HT)1A autoreceptor adaptive changes in substance P (neurokinin 1) receptor knock-out mice mimic antidepressant-induced desensitization. J Neurosci 2001; 21: 8188–8197.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Bilkei-Gorzo A, Racz I, Michel K, Zimmer A . Diminished anxiety-, depression-related behaviors in mice with selective deletion of the Tac1 gene. J Neurosci 2002; 22: 10046–10052.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. El Yacoubi M, Ledent C, Parmentier M, Costentin J, Vaugeois JM . Adenosine A2A receptor knockout mice are partially protected against drug-induced catalepsy. Neuroreport 2001; 12: 983–986.

    Article  CAS  PubMed  Google Scholar 

  42. Caldarone BJ, Karthigeyan K, Picciotto MR . Behavioral responses to a tricyclic antidepressant in knockout mice lacking the Beta-2-subunit of nicotinic receptor. Program No. 136.1 2002 Abstract Viewer/Itinerary Planner. Society for Neuroscience: Washington, DC, 2002 (online).

    Google Scholar 

  43. Martin M, Ledent C, Parmentier M, Maldonado R, Valverde O . Involvement of CB1 cannabinoid receptors in emotional behaviour. Psychopharmacology (Berl) 2002; 159: 379–387.

    Article  CAS  Google Scholar 

  44. Gavioli EC, Marzola G, Guerrini R, Bertorelli R, Zucchini S, De Lima TC et al. Blockade of nociceptin/orphanin FQ-NOP receptor signalling produces antidepressant-like effects: pharmacological and genetic evidences from the mouse forced swimming test. Eur J Neurosci 2003; 17: 1987–1990.

    Article  CAS  PubMed  Google Scholar 

  45. Tschenett A, Singewald N, Carli M, Balducci C, Salchner P, Vezzani A et al. Reduced anxiety and improved stress coping ability in mice lacking NPY-Y2 receptors. Eur J Neurosci 2003; 18: 143–148.

    Article  PubMed  Google Scholar 

  46. Holmes A, Hollon TR, Gleason TC, Liu Z, Dreiling J, Sibley DR et al. Behavioral characterization of dopamine D5 receptor null mutant mice. Behav Neurosci 2001; 115: 1129–1144.

    Article  CAS  PubMed  Google Scholar 

  47. Montkowski A, Barden N, Wotjak C, Stec I, Ganster J, Meaney M et al. Long-term antidepressant treatment reduces behavioural deficits in transgenic mice with impaired glucocorticoid receptor function. J Neuroendocrinol 1995; 7: 841–845.

    Article  CAS  PubMed  Google Scholar 

  48. Groenink L, Dirks A, Verdouw PM, Schipholt M, Veening JG, van der Gugten J et al. HPA axis dysregulation in mice overexpressing corticotropin releasing hormone. Biol Psychiatry 2002; 51: 875–881.

    Article  CAS  PubMed  Google Scholar 

  49. van Gaalen MM, Stenzel-Poore MP, Holsboer F, Steckler T . Effects of transgenic overproduction of CRH on anxiety-like behaviour. Eur J Neurosci 2002; 15: 2007–2015.

    Article  PubMed  Google Scholar 

  50. Bale TL, Vale WW . Increased depression-like behaviors in corticotropin-releasing factor receptor-2-deficient mice: sexually dichotomous responses. J Neurosci 2003; 23: 5295–5301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Yamada K, Iida R, Miyamoto Y, Saito K, Sekikawa K, Seishima M et al. Neurobehavioral alterations in mice with a targeted deletion of the tumor necrosis factor-alpha gene: implications for emotional behavior. J Neuroimmunol 2000; 111: 131–138.

    Article  CAS  PubMed  Google Scholar 

  52. Calapai G, Crupi A, Firenzuoli F, Inferrera G, Ciliberto G, Parisi A et al. Interleukin-6 involvement in antidepressant action of Hypericum perforatum. Pharmacopsychiatry 2001; 34(Suppl 1): S8–S10.

    Article  CAS  PubMed  Google Scholar 

  53. Svenningsson P, Tzavara ET, Witkin JM, Fienberg AA, Nomikos GG, Greengard P . Involvement of striatal and extrastriatal DARPP-32 in biochemical and behavioral effects of fluoxetine (Prozac). Proc Natl Acad Sci USA 2002; 99: 3182–3187.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Zhang HT, Huang Y, Jin SL, Frith SA, Suvarna N, Conti M et al. Antidepressant-like profile and reduced sensitivity to rolipram in mice deficient in the PDE4D phosphodiesterase enzyme. Neuropsychopharmacology 2002; 27: 587–595.

    CAS  PubMed  Google Scholar 

  55. Cao BJ, Li Y . Reduced anxiety—and depression-like behaviors in Emx1 homozygous mutant mice. Brain Res 2002; 937: 32–40.

    Article  CAS  PubMed  Google Scholar 

  56. Saarelainen T, Hendolin P, Lucas G, Koponen E, Sairanen M, MacDonald E et al. Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects. J Neurosci 2003; 23: 349–357.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Pudiak CM, Rahman Z, Gold SJ, Neve RL, Barrot M, Nestler EJ . The involvement of RGS9-2 in depression and anxiety-like behavior. Program No. 644.17 2002 Abstract Viewer/Itinerary Planner. Society for Neuroscience: Washington, DC, 2002 (online).

    Google Scholar 

  58. Okuyama S, Sakagawa T, Sugiyama F, Fukamizu A, Murakami K . Reduction of depressive-like behavior in mice lacking angiotensinogen. Neurosci Lett 1999; 261: 167–170.

    Article  CAS  PubMed  Google Scholar 

  59. Stork O, Welzl H, Wolfer D, Schuster T, Mantei N, Stork S et al. Recovery of emotional behaviour in neural cell adhesion molecule (NCAM) null mutant mice through transgenic expression of NCAM180. Eur J Neurosci 2000; 12: 3291–3306.

    Article  CAS  PubMed  Google Scholar 

  60. Shinohara T, Tomizuka K, Miyabara S, Takehara S, Kazuki Y, Inoue J et al. Mice containing a human chromosome 21 model behavioral impairment and cardiac anomalies of Down's syndrome. Hum Mol Genet 2001; 10: 1163–1175.

    Article  CAS  PubMed  Google Scholar 

  61. Nolan PM, Peters J, Strivens M, Rogers D, Hagan J, Spurr N et al. A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse. Nat Genet 2000; 25: 440–443.

    Article  CAS  PubMed  Google Scholar 

  62. Moldin SO, Farmer ME, Chin HR, Battey Jr JF . Trans-NIH neuroscience initiatives on mouse phenotyping, mutagenesis. Mamm Genome 2001; 12: 575–581.

    Article  CAS  PubMed  Google Scholar 

  63. Schafer WR . How do antidepressants work? Prospects for genetic analysis of drug mechanisms. Cell 1999; 98: 551–554.

    Article  CAS  PubMed  Google Scholar 

  64. McKinney WT . Overview of the past contributions of animal models and their changing place in psychiatry. Semin Clin Neuropsychiatry 2001; 6: 68–78.

    Article  CAS  PubMed  Google Scholar 

  65. Crawley JN . Whats Wrong with my Mouse? Behavioral Phenotyping of Transgenic and Knockout Mice. Wiley-Liss: New York, 2000.

    Google Scholar 

  66. Crawley JN, Paylor R . A proposed test battery and constellations of specific behavioral paradigms to investigate the behavioral phenotypes of transgenic and knockout mice. Horm Behav 1997; 31: 197–211.

    Article  CAS  PubMed  Google Scholar 

  67. Gold LH . Hierarchical strategy for phenotypic analysis in mice. Psychopharmacology (Berl) 1999; 147: 2–4.

    Article  CAS  Google Scholar 

  68. Rogers DC, Fisher EM, Brown SD, Peters J, Hunter AJ, Martin JE . Behavioral and functional analysis of mouse phenotype: SHIRPA, a proposed protocol for comprehensive phenotype assessment. Mamm Genome 1997; 8: 711–713.

    Article  CAS  PubMed  Google Scholar 

  69. Lucki I . A prescription to resist proscriptions for murine models of depression. Psychopharmacology (Berl) 2001; 153: 395–398.

    Article  CAS  Google Scholar 

  70. Association TAP . Diagnostic and Statistical Manual of Mental Disorders, 4th edn. American Psychiatric Press: Washington, DC, 1994.

    Google Scholar 

  71. Hamilton M . A rating scale for depression. J Neurol Neurosurg Psychiatry 1970; 23: 51–56.

    Google Scholar 

  72. Nesse RM . Is depression an adaptation? Arch Gen Psychiatry 2000; 57: 14–20.

    Article  CAS  PubMed  Google Scholar 

  73. Jones I, Blackshaw JK . An evolutionary approach to psychiatry. Aust N Z J Psychiatry 2000; 34: 8–13.

    Article  CAS  PubMed  Google Scholar 

  74. Dubrovsky B . Evolutionary psychiatry. Adaptationist and nonadaptationist conceptualizations. Prog Neuropsychopharmacol Biol Psychiatry 2002; 26: 1–19.

    Article  PubMed  Google Scholar 

  75. McLoughlin G . Is depression normal in human beings? A critique of the evolutionary perspective. Int J Ment Health Nurs 2002; 11: 170–173.

    Article  PubMed  Google Scholar 

  76. Gilliss B, Malanga CJ, Pieper JO, Carlezon Jr WA . Cocaine, SKF-82958 potentiate brain stimulation reward in Swiss–Webster mice. Psychopharmacology (Berl) 2002; 163: 238–248.

    Article  CAS  Google Scholar 

  77. Kokkinidis L, Zacharko RM, Anisman H . Amphetamine withdrawal: a behavioral evaluation. Life Sci 1986; 38: 1617–1623.

    Article  CAS  PubMed  Google Scholar 

  78. El-Ghundi M, O'Dowd BF, Erclik M, George SR . Attenuation of sucrose reinforcement in dopamine D1 receptor deficient mice. Eur J Neurosci 2003; 17: 851–862.

    Article  PubMed  Google Scholar 

  79. Nonogaki K, Strack AM, Dallman MF, Tecott LH . Leptin-independent hyperphagia, type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene. Nat Med 1998; 4: 1152–1156.

    Article  CAS  PubMed  Google Scholar 

  80. Karolyi IJ, Burrows HL, Ramesh TM, Nakajima M, Lesh JS, Seong E et al. Altered anxiety, weight gain in corticotropin-releasing hormone-binding protein-deficient mice. Proc Natl Acad Sci USA 1999; 96: 11595–11600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Boutrel B, Franc B, Hen R, Hamon M, Adrien J . Key role of 5-HT1B receptors in the regulation of paradoxical sleep as evidenced in 5-HT1B knock-out mice. J Neurosci 1999; 19: 3204–3212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. El Yacoubi M, Bouali S, Popa D, Naudon L, Leroux-Nicollet I, Hamon M et al. Behavioral, neurochemical, and electrophysiological characterization of a genetic mouse model of depression. Proc Natl Acad Sci USA 2003; 100: 6227–6232.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Wahlsten D, Metten P, Phillips TJ, Boehm II SL, Burkhart-Kasch S, Dorow J et al. Different data from different labs: lessons from studies of gene–environment interaction. J Neurobiol 2003; 54: 283–311.

    Article  PubMed  Google Scholar 

  84. Kafkafi N, Pagis M, Lipkind D, Mayo CL, Bemjamini Y, Golani I et al. Darting behavior: a quantitative movement pattern designed for discrimination and replicability in mouse locomotor behavior. Behav Brain Res 2003; 142: 193–205.

    Article  PubMed  Google Scholar 

  85. Mizoguchi K, Yuzurihara M, Ishige A, Sasaki H, Tabira T . Chronic stress impairs rotarod performance in rats: implications for depressive state. Pharmacol Biochem Behav 2002; 71: 79–84.

    Article  CAS  PubMed  Google Scholar 

  86. Dixon AK, Huber C, Lowe DA . Clozapine promotes approach-oriented behavior in male mice. J Clin Psychiatry 1994; 55(Suppl B): 4–7.

    PubMed  Google Scholar 

  87. Nonogaki K, Abdallah L, Goulding EH, Bonasera SJ, Tecott LH . Hyperactivity, reduced energy cost of physical activity in serotonin 5-HT(2C) receptor mutant mice. Diabetes 2003; 52: 315–320.

    Article  CAS  PubMed  Google Scholar 

  88. Grippo AJ, Beltz TG, Johnson AK . Behavioral, cardiovascular changes in the chronic mild stress model of depression. Physiol Behav 2003; 78: 703–710.

    Article  CAS  PubMed  Google Scholar 

  89. Dunn AL, Crnic LS . Repeated injections of interferon-alpha A/D in Balb/c mice: behavioral effects. Brain Behav Immun 1993; 7: 104–111.

    Article  CAS  PubMed  Google Scholar 

  90. Ballard TM, Pauly-Evers M, Higgins GA, Ouagazzal AM, Mutel V, Borroni E et al. Severe impairment of NMDA receptor function in mice carrying targeted point mutations in the glycine binding site results in drug-resistant nonhabituating hyperactivity. J Neurosci 2002; 22: 6713–6723.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Cheeta S, Ruigt G, van Proosdij J, Willner P . Changes in sleep architecture following chronic mild stress. Biol Psychiatry 1997; 41: 419–427.

    Article  CAS  PubMed  Google Scholar 

  92. Estape N, Steckler T . Cholinergic blockade impairs performance in operant DNMTP in two inbred strains of mice. Pharmacol Biochem Behav 2002; 72: 319–334.

    Article  CAS  PubMed  Google Scholar 

  93. Contarino A, Dellu F, Koob GF, Smith GW, Lee KF, Vale W et al. Reduced anxiety-like and cognitive performance in mice lacking the corticotropin-releasing factor receptor 1. Brain Res 1999; 835: 1–9.

    Article  CAS  PubMed  Google Scholar 

  94. van Gaalen MM, Stenzel-Poore M, Holsboer F, Steckler T . Reduced attention in mice overproducing corticotropin-releasing hormone. Behav Brain Res 2003; 142: 69–79.

    Article  CAS  PubMed  Google Scholar 

  95. Anisman H, Zacharko RM . Multiple neurochemical, behavioral consequences of stressors: implications for depression. Pharmacol Ther 1990; 46: 119–136.

    Article  CAS  PubMed  Google Scholar 

  96. Kessler RC . The effects of stressful life events on depression. Annu Rev Psychol 1997; 48: 191–214.

    Article  CAS  PubMed  Google Scholar 

  97. Sullivan PF, Neale MC, Kendler KS . Genetic epidemiology of major depression: review, meta-analysis. Am J Psychiatry 2000; 157: 1552–1562.

    Article  CAS  PubMed  Google Scholar 

  98. Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM Neurobiology of depression. Neuron 2002; 34: 13–25.

    Article  CAS  PubMed  Google Scholar 

  99. Connor TJ, Leonard BE . Biological markers of depression. In: Stanga CY (ed). Handbook of Experimental Pharmacology, Antidepressants: Current and Future Perspectives. Springer Verlag: New York, 2003.

    Google Scholar 

  100. Sachar EJ, Hellman L, Fukushima DK, Gallagher TF . Cortisol production in depressive illness. A clinical, biochemical clarification. Arch Gen Psychiatry 1970; 23: 289–298.

    Article  CAS  PubMed  Google Scholar 

  101. Nemeroff CB . Clinical significance of psychoneuroendocrinology in psychiatry: focus on the thyroid and adrenal. J Clin Psychiatry 1989; 50(Suppl): 13–20, discussion 21–22.

    PubMed  Google Scholar 

  102. Rubin RT, Phillips JJ . Adrenal gland enlargement in major depression. Arch Gen Psychiatry 1993; 50: 833–835.

    Article  CAS  PubMed  Google Scholar 

  103. Nemeroff CB, Krishnan KR, Reed D, Leder R, Beam C, Dunnick NR . Adrenal gland enlargement in major depression. A computed tomographic study. Arch Gen Psychiatry 1992; 49: 384–387.

    Article  CAS  PubMed  Google Scholar 

  104. Veenema AH, Meijer OC, de Kloet ER, Koolhaas JM, Bohus BG . Differences in basal and stress-induced HPA regulation of wild house mice selected for high and low aggression. Horm Behav 2003; 43: 197–204.

    Article  CAS  PubMed  Google Scholar 

  105. Beckmann N, Gentsch C, Baumann D, Bruttel K, Vassout A, Schoeffter P et al. Non-invasive, quantitative assessment of the anatomical phenotype of corticotropin-releasing factor-overexpressing mice by MRI. NMR Biomed 2001; 14: 210–216.

    Article  CAS  PubMed  Google Scholar 

  106. Carroll B . The dexamethasone suppression test for melancholia. Br J Psychiatry 1982; 140: 292–304.

    Article  CAS  PubMed  Google Scholar 

  107. Barden N, Stec IS, Montkowski A, Holsboer F, Reul JM . Endocrine profile, neuroendocrine challenge tests in transgenic mice expressing antisense RNA against the glucocorticoid receptor. Neuroendocrinology 1997; 66: 212–220.

    Article  CAS  PubMed  Google Scholar 

  108. Stec I, Barden N, Reul JM, Holsboer F . Dexamethasone nonsuppression in transgenic mice expressing antisense RNA to the glucocorticoid receptor. J Psychiatr Res 1994; 28: 1–5.

    Article  CAS  PubMed  Google Scholar 

  109. Bissette G, Klimek V, Pan J, Stockmeier C, Ordway G . Elevated concentrations of CRF in the locus coeruleus of depressed subjects. Neuropsychopharmacology 2003; 28: 1328–1335.

    Article  CAS  PubMed  Google Scholar 

  110. Nemeroff CB, Owens MJ, Bissette G, Andorn AC, Stanley M . Reduced corticotropin releasing factor binding sites in the frontal cortex of suicide victims. Arch Gen Psychiatry 1988; 45: 577–579.

    Article  CAS  PubMed  Google Scholar 

  111. Purba JS, Hoogendijk WJ, Hofman MA, Swaab DF . Increased number of vasopressin-, oxytocin-expressing neurons in the paraventricular nucleus of the hypothalamus in depression. Arch Gen Psychiatry 1996; 53: 137–143.

    Article  CAS  PubMed  Google Scholar 

  112. Makino S, Smith MA, Gold PW . Increased expression of corticotropin-releasing hormone, vasopressin messenger ribonucleic acid (mRNA) in the hypothalamic paraventricular nucleus during repeated stress: association with reduction in glucocorticoid receptor mRNA levels. Endocrinology 1995; 136: 3299–3309.

    Article  CAS  PubMed  Google Scholar 

  113. Stockmeier CA, Shapiro LA, Dilley GE, Kolli TN, Friedman L, Rajkowska G . Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression-postmortem evidence for decreased serotonin activity. J Neurosci 1998; 18: 7394–7401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Li Q, Wichems C, Heils A, Lesch KP, Murphy DL . Reduction in the density, expression, but not G-protein coupling, of serotonin receptors (5-HT1A) in 5-HT transporter knock-out mice: gender and brain region differences. J Neurosci 2000; 20: 7888–7895.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Arango V, Ernsberger P, Marzuk PM, Chen JS, Tierney H, Stanley M et al. Autoradiographic demonstration of increased serotonin 5-HT2, beta-adrenergic receptor binding sites in the brain of suicide victims. Arch Gen Psychiatry 1990; 47: 1038–1047.

    Article  CAS  PubMed  Google Scholar 

  116. Mudunkotuwa NT, Horton RW . Desipramine administration in the olfactory bulbectomized rat: changes in brain beta-adrenoceptor, 5-HT2A binding sites, their relationship to behaviour. Br J Pharmacol 1996; 117: 1481–1486.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Maj J, Rogoz Z . Pharmacological effects of venlafaxine, a new antidepressant, given repeatedly, on the alpha 1-adrenergic, dopamine and serotonin systems. J Neural Transm 1999; 106: 197–211.

    Article  CAS  PubMed  Google Scholar 

  118. Nakagawasai O, Tadano T, Arai Y, Hozumi S, Oba A, Tan-No K et al. Enhancement of 5-hydroxytryptamine-induced head-twitch response after olfactory bulbectomy. Neuroscience 2003; 117: 1017–1023.

    Article  CAS  PubMed  Google Scholar 

  119. Pirker W, Asenbaum S, Kasper S, Walter H, Angelberger P, Koch G et al. β-CIT SPECT demonstrates blockade of 5HT-uptake sites by citalopram in the human brain in vivo. J Neural Transm [Gen Sect] 1995; 100: 247–250.

    Article  CAS  Google Scholar 

  120. Tauscher J, Pirker W, de Zwaan M, Asenbaum S, Brucke T, Kasper S . In vivo visualization of serotonin transporters in the human brain during fluoxetine treatment. Eur Neuropsychopharmacol 1999; 9: 177–179.

    Article  CAS  PubMed  Google Scholar 

  121. Scheffel U, Kim S, Cline EJ, Kuhar MJ . Occupancy of the serotonin transporter by fluoxetine, paroxetine, and sertraline: in vivo studies with [125I]RTI-55. Synapse 1994; 16: 263–268.

    Article  CAS  PubMed  Google Scholar 

  122. Benmansour S, Owens WA, Cecchi M, Morilak DA, Frazer A . Serotonin clearance in vivo is altered to a greater extent by antidepressant-induced downregulation of the serotonin transporter than by acute blockade of this transporter. J Neurosci 2002; 22: 6766–6772.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Zanko M, Beigon A . Increased adrenergic receptor binding in human frontal cortex of suicide victims. Annual Meeting of Society for Neuroscience 1983 (Abstract no. 210.5.13).

  124. Vetulani J, Sulser F . Action of various antidepressant treatments reduces reactivity of noradrenergic cyclic AMP-generating system in limbic forebrain. Nature 1975; 257: 495–496.

    Article  CAS  PubMed  Google Scholar 

  125. Meana JJ, Barturen F, Garcia-Sevilla JA . Alpha 2-adrenoceptors in the brain of suicide victims: increased receptor density associated with major depression. Biol Psychiatry 1992; 31: 471–490.

    Article  CAS  PubMed  Google Scholar 

  126. Spyraki C, Fibiger HC . Functional evidence for subsensitivity of noradrenergic alpha 2 receptors after chronic desipramine treatment. Life Sci 1980; 27: 1863–1867.

    Article  CAS  PubMed  Google Scholar 

  127. Ordway GA, Smith KS, Haycock JW . Elevated tyrosine hydroxylase in the locus coeruleus of suicide victims. J Neurochem 1994; 62: 680–685.

    Article  CAS  PubMed  Google Scholar 

  128. Komori K, Kunimi Y, Yamaoka K, Ito T, Kasahara Y, Nagatsu I . Semiquantitative analysis of immunoreactivities of tyrosine hydroxylase, aromatic L-amino acid decarboxylase in the locus coeruleus of desipramine-treated mice. Neurosci Lett 1992; 147: 197–200.

    Article  CAS  PubMed  Google Scholar 

  129. Klimek V, Stockmeier C, Overholser J, Meltzer HY, Kalka S, Dilley G et al. Reduced levels of norepinephrine transporters in the locus coeruleus in major depression. J Neurosci 1997; 17: 8451–8458.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Ordway GA, Schenk J, Stockmeier CA, May W, Klimek V . Elevated agonist binding to alpha2-adrenoceptors in the locus coeruleus in major depression. Biol Psychiatry 2003; 53: 315–323.

    Article  CAS  PubMed  Google Scholar 

  131. Kovachich GB, Frazer A, Aronson CE . Effect of chronic administration of antidepressants on alpha 2-adrenoceptors in the locus coeruleus, its projection fields in rat brain determined by quantitative autoradiography. Neuropsychopharmacology 1993; 8: 57–65.

    Article  CAS  PubMed  Google Scholar 

  132. D'Haenen HA, Bossuyt A . Dopamine D2 receptors in depression measured with single photon emission computed tomography. Biol Psychiatry 1994; 35: 128–132.

    Article  CAS  PubMed  Google Scholar 

  133. Shah PJ, Ogilvie AD, Goodwin GM, Ebmeier KP . Clinical, psychometric correlates of dopamine D2 binding in depression. Psychol Med 1997; 27: 1247–1256.

    Article  CAS  PubMed  Google Scholar 

  134. Klimek V, Schenck JE, Han H, Stockmeier CA, Ordway GA . Dopaminergic abnormalities in amygdaloid nuclei in major depression: a postmortem study. Biol Psychiatry 2002; 52: 740–748.

    Article  CAS  PubMed  Google Scholar 

  135. Meyer JH, Kruger S, Wilson AA, Christensen BK, Goulding VS, Schaffer A et al. Lower dopamine transporter binding potential in striatum during depression. Neuroreport 2001; 12: 4121–4125.

    Article  CAS  PubMed  Google Scholar 

  136. Isovich E, Engelmann M, Landgraf R, Fuchs E . Social isolation after a single defeat reduces striatal dopamine transporter binding in rats. Eur J Neurosci 2001; 13: 1254–1256.

    Article  CAS  PubMed  Google Scholar 

  137. Auer DP, Putz B, Kraft E, Lipinski B, Schill J, Holsboer F . Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study. Biol Psychiatry 2000; 47: 305–313.

    Article  CAS  PubMed  Google Scholar 

  138. Nowak G, Ordway GA, Paul IA . Alterations in the N-methyl-D-aspartate (NMDA) receptor complex in the frontal cortex of suicide victims. Brain Res 1995; 675: 157–164.

    Article  CAS  PubMed  Google Scholar 

  139. Nowak G, Li Y, Paul IA . Adaptation of cortical but not hippocampal NMDA receptors after chronic citalopram treatment. Eur J Pharmacol 1996; 295: 75–85.

    Article  CAS  PubMed  Google Scholar 

  140. Honig A, Bartlett JR, Bouras N, Bridges PK . Amino acid levels in depression: a preliminary investigation. J Psychiatr Res 1988; 22: 159–164.

    Article  CAS  PubMed  Google Scholar 

  141. Sanacora G, Mason GF, Rothman DL, Behar KL, Hyder F, Petroff OA et al. Reduced cortical gamma-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy. Arch Gen Psychiatry 1999; 56: 1043–1047.

    Article  CAS  PubMed  Google Scholar 

  142. Hargreaves R . Imaging substance P receptors (NK1) in the living human brain using positron emission tomography. J Clin Psychiatry 2002; 63(Suppl 11): 18–24.

    CAS  PubMed  Google Scholar 

  143. Sastre M, Escriba PV, Reis DJ, Garcia-Sevilla JA . Decreased number, immunoreactivity of I2-imidazoline receptors in the frontal cortex of suicide victims. Ann NY Acad Sci 1995; 763: 520–522.

    Article  CAS  PubMed  Google Scholar 

  144. Zhu H, Paul IA, McNamara M, Redmond A, Nowak G, Piletz JE . Chronic imipramine treatment upregulates IR2-imidazoline receptive sites in rat brain. Neurochem Int 1997; 30: 101–107.

    Article  CAS  PubMed  Google Scholar 

  145. Maes M, Bosmans E, Suy E, Minner B, Raus J . A further exploration of the relationships between immune parameters, the HPA-axis activity in depressed patients. Psychol Med 1991; 21: 313–320.

    Article  CAS  PubMed  Google Scholar 

  146. Kubera M, Basta-Kaim A, Holan V, Simbirtsev A, Roman A, Pigareva N et al. Effect of mild chronic stress, as a model of depression, on the immunoreactivity of C57BL/6 mice. Int J Immunopharmacol 1998; 20: 781–789.

    Article  CAS  PubMed  Google Scholar 

  147. Maes M, Bosmans E, Suy E, Minner B, Raus J . Impaired lymphocyte stimulation by mitogens in severely depressed patients. A complex interface with HPA-axis hyperfunction, noradrenergic activity, the ageing process. Br J Psychiatry 1989; 155: 793–798.

    Article  CAS  PubMed  Google Scholar 

  148. Kubera M, Simbirtsev A, Mathison R, Maes M . Effects of repeated fluoxetine, citalopram administration on cytokine release in C57BL/6 mice. Psychiatry Res 2000; 96: 255–266.

    Article  CAS  PubMed  Google Scholar 

  149. Maes M, Bosmans E, Suy E, Vandervorst C, DeJonckheere C, Raus J . Depression-related disturbances in mitogen-induced lymphocyte responses, interleukin-1 beta, soluble interleukin-2 receptor production. Acta Psychiatr Scand 1991; 84: 379–386.

    Article  CAS  PubMed  Google Scholar 

  150. Maes M, Scharpe S, Meltzer HY, Bosmans E, Suy E, Calabrese J et al. Relationships between interleukin-6 activity, acute phase proteins, and function of the hypothalamic-pituitary-adrenal axis in severe depression. Psychiatry Res 1993; 49: 11–27.

    Article  CAS  PubMed  Google Scholar 

  151. Song C, Dinan T, Leonard BE . Changes in immunoglobulin, complement, acute phase protein levels in the depressed patients, normal controls. J Affect Disord 1994; 30: 283–288.

    Article  CAS  PubMed  Google Scholar 

  152. Seidel A, Arolt V, Hunstiger M, Rink L, Behnisch A, Kirchner H . Cytokine production, serum proteins in depression. Scand J Immunol 1995; 41: 534–538.

    Article  CAS  PubMed  Google Scholar 

  153. Kubera M, Symbirtsev A, Basta-Kaim A, Borycz J, Roman A, Papp M et al. Effect of chronic treatment with imipramine on interleukin 1, interleukin 2 production by splenocytes obtained from rats subjected to a chronic mild stress model of depression. Pol J Pharmacol 1996; 48: 503–506.

    CAS  PubMed  Google Scholar 

  154. Maes M . Major depression, activation of the inflammatory response system. Adv Exp Med Biol 1999; 461: 25–46.

    Article  CAS  PubMed  Google Scholar 

  155. Kubera M, Holan V, Mathison R, Maes M . The effect of repeated amitriptyline, desipramine administration on cytokine release in C57BL/6 mice. Psychoneuroendocrinology 2000; 25: 785–797.

    Article  CAS  PubMed  Google Scholar 

  156. Dowlatshahi D, MacQueen GM, Wang JF, Reiach JS, Young LT . G Protein-coupled cyclic AMP signaling in postmortem brain of subjects with mood disorders: effects of diagnosis, suicide, treatment at the time of death. J Neurochem 1999; 73: 1121–1126.

    Article  CAS  PubMed  Google Scholar 

  157. Yamada S, Yamamoto M, Ozawa H, Riederer P, Saito T . Reduced phosphorylation of cyclic AMP-responsive element binding protein in the postmortem orbitofrontal cortex of patients with major depressive disorder. J Neural Transm 2003; 110: 671–680.

    Article  CAS  PubMed  Google Scholar 

  158. Thome J, Sakai N, Shin K, Steffen C, Zhang YJ, Impey S et al. cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment. J Neurosci 2000; 20: 4030–4036.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Nibuya M, Nestler EJ, Duman RS . Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus. J Neurosci 1996; 16: 2365–2372.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Chen B, Dowlatshahi D, MacQueen GM, Wang JF, Young LT . Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry 2001; 50: 260–265.

    Article  CAS  PubMed  Google Scholar 

  161. Conti AC, Cryan JF, Dalvi A, Lucki I, Blendy JA . cAMP response element-binding protein is essential for the upregulation of brain-derived neurotrophic factor transcription, but not the behavioral or endocrine responses to antidepressant drugs. J Neurosci 2002; 22: 3262–3268.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Karege F, Perret G, Bondolfi G, Schwald M, Bertschy G, Aubry JM . Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res 2002; 109: 143–148.

    Article  CAS  PubMed  Google Scholar 

  163. Bayer TA, Schramm M, Feldmann N, Knable MB, Falkai P . Antidepressant drug exposure is associated with mRNA levels of tyrosine receptor kinase B in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 2000; 24: 881–888.

    Article  CAS  PubMed  Google Scholar 

  164. Lechin F, van der Dijs B, Orozco B, Lechin ME, Baez S, Lechin AE et al. Plasma neurotransmitters, blood pressure, and heart rate during supine-resting, orthostasis, and moderate exercise conditions in major depressed patients. Biol Psychiatry 1995; 38: 166–173.

    Article  CAS  PubMed  Google Scholar 

  165. Carney RM, Rich MW, teVelde A, Saini J, Clark K, Freedland KE . The relationship between heart rate, heart rate variability, depression in patients with coronary artery disease. J Psychosom Res 1988; 32: 159–164.

    Article  CAS  PubMed  Google Scholar 

  166. Bouwknecht JA, Hijzen TH, van der Gugten J, Maes RA, Hen R, Olivier B . 5-HT(1B) receptor knockout mice show no adaptive changes in 5-HT(1A) receptor function as measured telemetrically on body temperature and heart rate responses. Brain Res Bull 2002; 57: 93–102.

    Article  CAS  PubMed  Google Scholar 

  167. Krittayaphong R, Cascio WE, Light KC, Sheffield D, Golden RN, Finkel JB et al. Heart rate variability in patients with coronary artery disease: differences in patients with higher and lower depression scores. Psychosom Med 1997; 59: 231–235.

    Article  CAS  PubMed  Google Scholar 

  168. Casper RC, Redmond Jr. DE, Katz MM, Schaffer CB, Davis JM, Koslow SH . Somatic symptoms in primary affective disorder. Presence and relationship to the classification of depression. Arch Gen Psychiatry 1985; 42: 1098–1104.

    Article  CAS  PubMed  Google Scholar 

  169. Michael A, O'Keane V . Sexual dysfunction in depression. Hum Psychopharmacol 2000; 15: 337–345.

    Article  PubMed  Google Scholar 

  170. Nofzinger EA, Schwartz RM, Reynolds III CF, Thase ME, Jennings JR, Frank E et al. Correlation of nocturnal penile tumescence and daytime affect intensity in depressed men. Psychiatry Res 1993; 49: 139–150.

    Article  CAS  PubMed  Google Scholar 

  171. Rissman EF, Wersinger SR, Fugger HN, Foster TC . Sex with knockout models: behavioral studies of estrogen receptor alpha. Brain Res 1999; 835: 80–90.

    Article  CAS  PubMed  Google Scholar 

  172. Brotto LA, Gorzalka BB, LaMarre AK . Melatonin protects against the effects of chronic stress on sexual behaviour in male rats. Neuroreport 2001; 12: 3465–3469.

    Article  CAS  PubMed  Google Scholar 

  173. Sheline YI . Hippocampal atrophy in major depression: a result of depression-induced neurotoxicity? Mol Psychiatry 1996; 1: 298–299.

    CAS  PubMed  Google Scholar 

  174. Bremner JD, Narayan M, Anderson ER, Staib LH, Miller HL, Charney DS . Hippocampal volume reduction in major depression. Am J Psychiatry 2000; 157: 115–118.

    Article  CAS  PubMed  Google Scholar 

  175. Steffens DC, Byrum CE, McQuoid DR, Greenberg DL, Payne ME, Blitchington TF et al. Hippocampal volume in geriatric depression. Biol Psychiatry 2000; 48: 301–309.

    Article  CAS  PubMed  Google Scholar 

  176. Czeh B, Michaelis T, Watanabe T, Frahm J, de Biurrun G, van Kampen M et al. Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proc Natl Acad Sci USA 2001; 98: 12796–12801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. MacQueen GM, Campbell S, McEwen BS, Macdonald K, Amano S, Joffe RT et al. Course of illness, hippocampal function, and hippocampal volume in major depression. Proc Natl Acad Sci USA 2003; 100: 1387–1392.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Rajkowska G . Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Biol Psychiatry 2000; 48: 766–777.

    Article  CAS  PubMed  Google Scholar 

  179. Rajkowska G, Halaris A, Selemon LD . Reductions in neuronal and glial density characterize the dorsolateral prefrontal cortex in bipolar disorder. Biol Psychiatry 2001; 49: 741–752.

    Article  CAS  PubMed  Google Scholar 

  180. Rajkowska G, Miguel-Hidalgo JJ, Wei J, Dilley G, Pittman SD, Meltzer HY et al. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry 1999; 45: 1085–1098.

    Article  CAS  PubMed  Google Scholar 

  181. Wellman CL . Dendritic reorganization in pyramidal neurons in medial prefrontal cortex after chronic corticosterone administration. J Neurobiol 2001; 49: 245–253.

    Article  CAS  PubMed  Google Scholar 

  182. Frodl T, Meisenzahl E, Zetzsche T, Bottlender R, Born C, Groll C et al. Enlargement of the amygdala in patients with a first episode of major depression. Biol Psychiatry 2002; 51: 708–714.

    Article  PubMed  Google Scholar 

  183. Vyas A, Bernal S, Chattarji S . Effects of chronic stress on dendritic arborization in the central, extended amygdala. Brain Res 2003; 965: 290–294.

    Article  CAS  PubMed  Google Scholar 

  184. Kellner CH, Rubinow DR, Post RM . Cerebral ventricular size and cognitive impairment in depression. J Affect Disord 1986; 10: 215–219.

    Article  CAS  PubMed  Google Scholar 

  185. Beats B, Levy R, Forstl H . Ventricular enlargement, caudate hyperdensity in elderly depressives. Biol Psychiatry 1991; 30: 452–458.

    Article  CAS  PubMed  Google Scholar 

  186. Wrynn AS, Mac Sweeney CP, Franconi F, Lemaire L, Pouliquen D, Herlidou S et al. An in-vivo magnetic resonance imaging study of the olfactory bulbectomized rat model of depression. Brain Res 2000; 879: 193–199.

    Article  CAS  PubMed  Google Scholar 

  187. Davidson RJ, Pizzagalli D, Nitschke JB, Putnam K . Depression: perspectives from affective neuroscience. Annu Rev Psychol 2002; 53: 545–574.

    Article  PubMed  Google Scholar 

  188. Drevets WC . Neuroimaging studies of mood disorders. Biol Psychiatry 2000; 48: 813–829.

    Article  CAS  PubMed  Google Scholar 

  189. Mayberg HS . Modulating limbic-cortical circuits in depression: targets of antidepressant treatments. Semin Clin Neuropsychiatry 2002; 7: 255–268.

    Article  PubMed  Google Scholar 

  190. Mayberg HS . Limbic-cortical dysregulation: a proposed model of depression. J Neuropsychiatry Clin Neurosci 1997; 9: 471–481.

    Article  CAS  PubMed  Google Scholar 

  191. Lahti KM, Ferris CF, Li F, Sotak CH, King JA . Imaging brain activity in conscious animals using functional MRI. J Neurosci Methods 1998; 82: 75–83.

    Article  CAS  PubMed  Google Scholar 

  192. Davidson RJ, Irwin W, Anderle MJ, Kalin NH . The neural substrates of affective processing in depressed patients treated with venlafaxine. Am J Psychiatry 2003; 160: 64–75.

    Article  PubMed  Google Scholar 

  193. Cook IA, Leuchter AF, Morgan M, Witte E, Stubbeman WF, Abrams M et al. Early changes in prefrontal activity characterize clinical responders to antidepressants. Neuropsychopharmacology 2002; 27: 120–131.

    Article  CAS  PubMed  Google Scholar 

  194. Bremner JD, Vythilingam M, Vermetten E, Nazeer A, Adil J, Khan S et al. Reduced volume of orbitofrontal cortex in major depression. Biol Psychiatry 2002; 51: 273–279.

    Article  PubMed  Google Scholar 

  195. Spring B, Pingitore R, McChargue DE . Reward value of cigarette smoking for comparably heavy smoking schizophrenic, depressed, and nonpatient smokers. Am J Psychiatry 2003; 160: 316–322.

    Article  PubMed  Google Scholar 

  196. Lerman C, Audrain J, Orleans CT, Boyd R, Gold K, Main D et al. Investigation of mechanisms linking depressed mood to nicotine dependence. Addict Behav 1996; 21: 9–19.

    Article  CAS  PubMed  Google Scholar 

  197. Markou A, Kenny PJ . Neuroadaptations to chronic exposure to drugs of abuse: relevance to depressive symptomatology seen across psychiatric diagnostic categories. Neurotox Res 2002; 4: 297–313.

    Article  PubMed  Google Scholar 

  198. Tremblay LK, Naranjo CA, Cardenas L, Herrmann N, Busto UE . Probing brain reward system function in major depressive disorder: altered response to dextroamphetamine. Arch Gen Psychiatry 2002; 59: 409–416.

    Article  PubMed  Google Scholar 

  199. Lin D, Bruijnzeel AW, Schmidt P, Markou A . Exposure to chronic mild stress alters thresholds for lateral hypothalamic stimulation reward, subsequent responsiveness to amphetamine. Neuroscience 2002; 114: 925–933.

    Article  CAS  PubMed  Google Scholar 

  200. Holmes PV, Masini CV, Primeaux SD, Garrett JL, Zellner A, Stogner KS et al. Intravenous self-administration of amphetamine is increased in a rat model of depression. Synapse 2002; 46: 4–10.

    Article  CAS  PubMed  Google Scholar 

  201. McKinney WTJ, Bunney WEJ . Animal model of depression. I. Review of evidence: implications for research. Arch Gen Psychiatry 1969; 21: 240–248.

    Article  PubMed  Google Scholar 

  202. Willner P . Animal models of depression: an overview. Pharmacol Ther 1990; 45: 425–455.

    Article  CAS  PubMed  Google Scholar 

  203. Willner P, Mitchell PJ . The validity of animal models of predisposition to depression. Behav Pharmacol 2002; 13: 169–188.

    Article  CAS  PubMed  Google Scholar 

  204. Geyer MA, Markou A . The role of preclinical models in the development of psychotropic drugs. In: Kupfer DJ (ed). Psychopharmacology: The Fifth Generation of Progress. Raven: New York, 2000.

    Google Scholar 

  205. Geyer MA, Markou A . Animal models of psychiatric disorders. In: Bloom FE, Kupfer DJ (eds). Psychopharmacology: The Fourth Generation of Progress. Raven Press: Philadephia, PA, 1995 pp 787–798.

    Google Scholar 

  206. Sarter M, Bruno JP . Animal models in biological psychiatry. In: D'haenen H, den Boer JA, Westenberg H, Willner P (eds). Textbook of Biological Psychiatry. John Wiley & Sons: Boston, MA, 2002 pp 37–44.

    Chapter  Google Scholar 

  207. Hyman SE, Fenton WS . Medicine. What are the right targets for psychopharmacology? Science 2003; 299: 350–351.

    Article  CAS  PubMed  Google Scholar 

  208. Inoue K, Lupski JR . Genetics, genomics of behavioral, psychiatric disorders. Curr Opin Genet Dev 2003; 13: 303–309.

    Article  CAS  PubMed  Google Scholar 

  209. Gottesman II, Gould TD . The endophenotype concept in psychiatry: etymology, strategic intentions. Am J Psychiatry 2003; 160: 636–645.

    Article  PubMed  Google Scholar 

  210. Rush AJ, Ryan ND . Current and emerging therapeutics for depression. In: Nemeroff CB (ed). Neuropsychopharmacology: The Fifth Generation of Progress. Lippincott Williams & Wilkins: Philadelphia, PA, 2002.

    Google Scholar 

  211. Manning JS . Difficult-to-treat depressions: a primary care perspective. J Clin Psychiatry 2003; 64(Suppl 1): 24–31.

    PubMed  Google Scholar 

  212. Cryan JF, Markou A, Lucki I . Assessing antidepressant activity in rodents: recent developments, future needs. Trends Pharmacol Sci 2002; 23: 238–245.

    Article  CAS  PubMed  Google Scholar 

  213. Crabbe JC, Wahlsten D, Dudek BC . Genetics of mouse behavior: interactions with laboratory environment. Science 1999; 284: 1670–1672.

    Article  CAS  PubMed  Google Scholar 

  214. Wahlsten D, Rustay NR, Metten P, Crabbe JC . In search of a better mouse test. Trends Neurosci 2003; 26: 132–136.

    Article  CAS  PubMed  Google Scholar 

  215. Picciotto MR, Self DW . Testing the genetics of behavior in mice. Science 1999; 285: 2067, (author reply 2069–2070).

    Article  CAS  PubMed  Google Scholar 

  216. Sapolsky R . Genetic hyping. The Sciences 2000; March/April: 12–15.

  217. Cryan JF, Leonard BE . 5-HT1A, beyond: the role of serotonin, its receptors in depression, the antidepressant response. Hum Psychopharmacol 2000; 15: 113–135.

    Article  CAS  PubMed  Google Scholar 

  218. van der Staay FJ, Steckler T . Behavioural phenotyping of mouse mutants. Behav Brain Res 2001; 125: 3–12.

    Article  CAS  PubMed  Google Scholar 

  219. Wurbel H . Behavioral phenotyping enhances—beyond (environmental) standardization. Genes Brain Behav 2002; 1: 9–13.

    Article  Google Scholar 

  220. Porsolt RD, Le Pichon M, Jalfre M . Depression: a new animal model sensitive to antidepressant treatments. Nature 1977; 266: 730–732.

    Article  CAS  PubMed  Google Scholar 

  221. Lucki I . The forced swimming test as a model for core, component behavioral effects of antidepressant drugs. Behav Pharmacol 1997; 8: 523–532.

    Article  CAS  PubMed  Google Scholar 

  222. Cryan JF, Lucki I . Antidepressant-like behavioral effects mediated by 5-hydroxytryptamine(2C) receptors. J Pharmacol Exp Ther 2000; 295: 1120–1126.

    CAS  PubMed  Google Scholar 

  223. Cryan JF, Lucki I . 5-HT4 receptors do not mediate the antidepressant-like behavioral effects of fluoxetine in a modified forced swim test. Eur J Pharmacol 2000; 409: 295–299.

    Article  CAS  PubMed  Google Scholar 

  224. Shekhar A, McCann UD, Meaney MJ, Blanchard DC, Davis M, Frey KA et al. Summary of a National Institute of Mental Health workshop: developing animal models of anxiety disorders. Psychopharmacology (Berl) 2001; 157: 327–339.

    Article  CAS  Google Scholar 

  225. Blanchard DC, Griebel G, Blanchard RJ . The Mouse Defense Test Battery: pharmacological, behavioral assays for anxiety, panic. Eur J Pharmacol 2003; 463: 97–116.

    Article  CAS  PubMed  Google Scholar 

  226. Sullivan GM, Apergis J, Gorman JM, LeDoux JE . Rodent doxapram model of panic: behavioral effects, c-Fos immunoreactivity in the amygdala. Biol Psychiatry 2003; 53: 863–870.

    Article  CAS  PubMed  Google Scholar 

  227. Grillon C, Cordova J, Levine LR, Morgan III CA . Anxiolytic effects of a novel group II metabotropic glutamate receptor agonist (LY354740) in the fear-potentiated startle paradigm in humans. Psychopharmacology (Berl) 2003; 168: 446–454.

    Article  CAS  Google Scholar 

  228. Vaugeois JM, Odievre C, Loisel L, Costentin J . A genetic mouse model of helplessness sensitive to imipramine. Eur J Pharmacol 1996; 316: R1–2.

    Article  CAS  PubMed  Google Scholar 

  229. Papaioannou A, Gerozissis K, Prokopiou A, Bolaris S, Stylianopoulou F . Sex differences in the effects of neonatal handling on the animal's response to stress, the vulnerability for depressive behaviour. Behav Brain Res 2002; 129: 131–139.

    Article  CAS  PubMed  Google Scholar 

  230. Solberg LC, Horton TH, Turek FW . Circadian rhythms, depression: effects of exercise in an animal model. Am J Physiol 1999; 276: R152–61.

    Article  CAS  PubMed  Google Scholar 

  231. Alcaro A, Cabib S, Ventura R, Puglisi-Allegra S . Genotype-, experience-dependent susceptibility to depressive-like responses in the forced-swimming test. Psychopharmacology (Berl) 2002; 164: 138–143.

    Article  CAS  Google Scholar 

  232. Tannenbaum B, Tannenbaum GS, Sudom K, Anisman H . Neurochemical, behavioral alterations elicited by a chronic intermittent stressor regimen: implications for allostatic load. Brain Res 2002; 953: 82–92.

    Article  CAS  PubMed  Google Scholar 

  233. Alonso SJ, Damas C, Navarro E . Behavioral despair in mice after prenatal stress. J Physiol Biochem 2000; 56: 77–82.

    Article  CAS  PubMed  Google Scholar 

  234. Galea LA, Wide JK, Barr AM . Estradiol alleviates depressive-like symptoms in a novel animal model of post-partum depression. Behav Brain Res 2001; 122: 1–9.

    Article  CAS  PubMed  Google Scholar 

  235. Makino M, Kitano Y, Hirohashi M, Takasuna K . Enhancement of immobility in mouse forced swimming test by treatment with human interferon. Eur J Pharmacol 1998; 356: 1–7.

    Article  CAS  PubMed  Google Scholar 

  236. Yamano M, Yuki H, Yasuda S, Miyata K . Corticotropin-releasing hormone receptors mediate consensus interferon-alpha YM643-induced depression-like behavior in mice. J Pharmacol Exp Ther 2000; 292: 181–187.

    CAS  PubMed  Google Scholar 

  237. Blokland A, Lieben C, Deutz NE . Anxiogenic, depressive-like effects, but no cognitive deficits, after repeated moderate tryptophan depletion in the rat. J Psychopharmacol 2002; 16: 39–49.

    Article  CAS  PubMed  Google Scholar 

  238. Anraku T, Ikegaya Y, Matsuki N, Nishiyama N . Withdrawal from chronic morphine administration causes prolonged enhancement of immobility in rat forced swimming test. Psychopharmacology (Berl) 2001; 157: 217–220.

    Article  CAS  Google Scholar 

  239. Noda Y, Kamei H, Mamiya T, Furukawa H, Nabeshima T . Repeated phencyclidine treatment induces negative symptom-like behavior in forced swimming test in mice: imbalance of prefrontal serotonergic, dopaminergic functions. Neuropsychopharmacology 2000; 23: 375–387.

    Article  CAS  PubMed  Google Scholar 

  240. Cryan JF, Hoyer D, Markou A . Withdrawal from chronic amphetamine induces depressive-like behavioral effects in rodents. Biol Psychiatry 2003; 54: 49–58.

    Article  CAS  PubMed  Google Scholar 

  241. Larm JA, Shen PJ, Gundlach AL . Differential galanin receptor-1, galanin expression by 5-HT neurons in dorsal raphe nucleus of rat, mouse: evidence for species-dependent modulation of serotonin transmission. Eur J Neurosci 2003; 17: 481–493.

    Article  PubMed  Google Scholar 

  242. Silva AJ, Simpson EM, Takahashi JS, Lipp H-P, Nakanishi S, Wehner JM et al. Mutant mice, neuroscience: recommendations concerning genetic background. Neuron 1997; 19: 755–759.

    Article  Google Scholar 

  243. Weissman MM, Klerman GL . Sex differences, the epidemiology of depression. Arch Gen Psychiatry 1977; 34: 98–111.

    Article  CAS  PubMed  Google Scholar 

  244. Kornstein SG . Gender differences in depression: implications for treatment. J Clin Psychiatry 1997; 58(Suppl 15): 12–18.

    PubMed  Google Scholar 

  245. Palanza P . Animal models of anxiety, depression: how are females different? Neurosci Biobehav Rev 2001; 25: 219–233.

    Article  CAS  PubMed  Google Scholar 

  246. Blanchard BA, Glick SD . Sex differences in mesolimbic dopamine responses to ethanol, relationship to ethanol intake in rats. Recent Dev Alcohol 1995; 12: 231–241.

    CAS  PubMed  Google Scholar 

  247. Archer J . Rodent sex differences in emotional, related behavior. Behav Biol 1975; 14: 451–479.

    Article  CAS  PubMed  Google Scholar 

  248. Gray JA, Buffery AW . Sex differences in emotional, cognitive behaviour in mammals including man: adaptive, neural bases. Acta Psychol (Amst) 1971; 35: 89–111.

    Article  CAS  Google Scholar 

  249. Perrot-Sinal T, Ossenkopp KP, Kavaliers M . Influence of a natural stressor (predator odor) on locomotor activity in the meadow vole (Microtus pennsylvanicus): modulation by sex, reproductive condition and gonadal hormones. Psychoneuroendocrinology 2000; 25: 259–276.

    Article  CAS  PubMed  Google Scholar 

  250. Dixon LK, Defries JC . Development of open field in mice: effects of age, experience. Dev Psychobiol 1968; 101–107.

  251. Stock HS, Ford K, Wilson MA . Gender, gonadal hormone effects in the olfactory bulbectomy animal model of depression. Pharmacol Biochem Behav 2000; 67: 183–191.

    Article  CAS  PubMed  Google Scholar 

  252. Stock HS, Hand GA, Ford K, Wilson MA . Changes in defensive behaviors following olfactory bulbectomy in male, female rats. Brain Res 2001; 903: 242–246.

    Article  CAS  PubMed  Google Scholar 

  253. David DJ, Nic Dhonnchadha BA, Jolliet P, Hascoet M, Bourin M . Are there gender differences in the temperature profile of mice after acute antidepressant administration, exposure to two animal models of depression? Behav Brain Res 2001; 119: 203–211.

    Article  CAS  PubMed  Google Scholar 

  254. Alonso SJ, Arevalo R, Afonso D, Rodriguez M . Effects of maternal stress during pregnancy on forced swimming test behavior of the offspring. Physiol Behav 1991; 50: 511–517.

    Article  CAS  PubMed  Google Scholar 

  255. Alonso SJ, Castellano MA, Quintero M, Navarro E . Action of antidepressant drugs on maternal stress-induced hypoactivity in female rats. Methods Find Exp Clin Pharmacol 1999; 21: 291–295.

    Article  CAS  PubMed  Google Scholar 

  256. Caldarone BJ, George TP, Zachariou V, Picciotto MR . Gender differences in learned helplessness behavior are influenced by genetic background. Pharmacol Biochem Behav 2000; 66: 811–817.

    Article  CAS  PubMed  Google Scholar 

  257. Caldarone BJ, Karthigeyan K, Harrist A, Hunsberger JG, Wittmack E, King SL et al. Sex differences in response to oral amitriptyline in three animal models of depression in C57BL/6J mice. Psychopharmacology (Berl) 2003; 170: 94–101.

    Article  CAS  Google Scholar 

  258. Brotto LA, Barr AM, Gorzalka BB . Sex differences in forced-swim, open-field test behaviours after chronic administration of melatonin. Eur J Pharmacol 2000; 402: 87–93.

    Article  CAS  PubMed  Google Scholar 

  259. Steenbergen HL, Heinsbroek RP, Van Hest A, Van de Poll NE . Sex-dependent effects of inescapable shock administration on shuttlebox-escape performance, elevated plus-maze behavior. Physiol Behav 1990; 48: 571–576.

    Article  CAS  PubMed  Google Scholar 

  260. Gorzalka BB, Hanson LA, Brotto LA . Chronic stress effects on sexual behavior in male, female rats: mediation by 5-HT2A receptors. Pharmacol Biochem Behav 1998; 61: 405–412.

    Article  CAS  PubMed  Google Scholar 

  261. Jones MD, Lucki I . Gender-specific role of serotonergic autoreceptor regulation in stress-induced depression. Abstract from 32nd Annual Meeting of Society for Neuroscience 2002 (online).

  262. Phillips TJ, Belknap JK, Hitzemann RJ, Buck KJ, Cunningham CL, Crabbe JC et al. Harnessing the mouse to unravel the genetics of human disease. Genes Brain Behav 2001; 1: 14–26.

    Article  Google Scholar 

  263. Flint J . Analysis of quantitative trait loci that influence animal behavior. J Neurobiol 2003; 54: 46–77.

    Article  CAS  PubMed  Google Scholar 

  264. Crabbe JC . Alcohol, genetics: new models. Am J Med Genet 2002; 114: 969–974.

    Article  PubMed  Google Scholar 

  265. Yoshikawa T, Watanabe A, Ishitsuka Y, Nakaya A, Nakatani N . Identification of multiple genetic loci linked to the propensity for ‘behavioral despair’ in mice. Genome Res 2002; 12: 357–366.

    Article  CAS  PubMed  Google Scholar 

  266. Shilling PD, Kelsoe JR . Functional genomics approaches to understanding brain disorders. Pharmacogenomics 2002; 3: 31–45.

    Article  CAS  PubMed  Google Scholar 

  267. Nestler EJ, Gould E, Manji H, Buncan M, Duman RS, Gershenfeld HK et al. Preclinical models: status of basic research in depression. Biol Psychiatry 2002; 52: 503–528.

    Article  PubMed  Google Scholar 

  268. Kinnunen AK, Koenig JI, Bilbe G . Repeated variable prenatal stress alters pre-, postsynaptic gene expression in the rat frontal pole. J Neurochem 2003; 86: 736–748.

    Article  CAS  PubMed  Google Scholar 

  269. Maccari S, Darnaudery M, Morley-Fletcher S, Zuena AR, Cinque C, Van Reeth O . Prenatal stress, long-term consequences: implications of glucocorticoid hormones. Neurosci Biobehav Rev 2003; 27: 119–127.

    Article  CAS  PubMed  Google Scholar 

  270. Porsolt RD . Animal models of depression: utility for transgenic research. Rev Neurosci 2000; 11: 53–58.

    Article  CAS  PubMed  Google Scholar 

  271. Seong E, Seasholtz AF, Burmeister M . Mouse models for psychiatric disorders. Trends Genet 2002; 18: 643–650.

    Article  CAS  PubMed  Google Scholar 

  272. Borsini F, Lecci A, Sessarego A, Frassine R, Meli A . Discovery of antidepressant activity by forced swimming test may depend on pre-exposure of rats to a stressful situation. Psychopharmacology (Berl) 1989; 97: 183–188.

    Article  CAS  Google Scholar 

  273. Borsini F, Meli A . Is the forced swimming test a suitable model for revealing antidepressant activity? Psychopharmacology (Berl) 1988; 94: 147–160.

    Article  CAS  Google Scholar 

  274. Lucki I, Dalvi A, Mayorga AJ . Sensitivity to the effects of pharmacologically selective antidepressants in different strains of mice. Psychopharmacology (Berl) 2001; 155: 315–322.

    Article  CAS  Google Scholar 

  275. Detke MJ, Johnson J, Lucki I . Acute, chronic antidepressant drug treatment in the rat forced swimming test model of depression. Exp Clin Psychopharmacol 1997; 5: 107–112.

    Article  CAS  PubMed  Google Scholar 

  276. Reneric JP, Bouvard M, Stinus L . In the rat forced swimming test, chronic but not subacute administration of dual 5-HT/NA antidepressant treatments may produce greater effects than selective drugs. Behav Brain Res 2002; 136: 521–532.

    Article  CAS  PubMed  Google Scholar 

  277. Rapaport MH . Prevalence, recognition, treatment of comorbid depression, anxiety. J Clin Psychiatry 2001; 62(Suppl 24): 6–10.

    PubMed  Google Scholar 

  278. Moller HJ . Anxiety associated with comorbid depression. J Clin Psychiatry 2002; 63(Suppl 14)): 22–26.

    CAS  PubMed  Google Scholar 

  279. Taghzouti K, Lamarque S, Kharouby M, Simon H . Interindividual differences in active, passive behaviors in the forced-swimming test: implications for animal models of psychopathology. Biol Psychiatry 1999; 45: 750–758.

    Article  CAS  PubMed  Google Scholar 

  280. Ho YJ, Eichendorff J, Schwarting RK . Individual response profiles of male Wistar rats in animal models for anxiety, depression. Behav Brain Res 2002; 136: 1–12.

    Article  PubMed  Google Scholar 

  281. Cryan JF, Page ME, Lucki I . Noradrenergic lesions differentially alter the antidepressant-like effects of reboxetine in a modified forced swim test. Eur J Pharmacol 2002; 436: 197–205.

    Article  CAS  PubMed  Google Scholar 

  282. Thierry B, Steru L, Chermat R, Simon P . Searching–waiting strategy: a candidate for an evolutionary model of depression? Behav Neural Biol 1984; 41: 180–189.

    Article  CAS  PubMed  Google Scholar 

  283. Dixon AK . Ethological strategies for defence in animals, humans: their role in some psychiatric disorders. Br J Med Psychol 1998; 71(Part 4): 417–445.

    Article  PubMed  Google Scholar 

  284. Gilbert P, Allan S . The role of defeat, entrapment (arrested flight) in depression: an exploration of an evolutionary view. Psychol Med 1998; 28: 585–598.

    Article  CAS  PubMed  Google Scholar 

  285. Weingartner H, Silberman E . Models of cognitive impairment: cognitive changes in depression. Psychopharmacol Bull 1982; 18: 27–42.

    CAS  PubMed  Google Scholar 

  286. Nishimura H, Tsuda A, Oguchi M, Ida Y, Tanaka M . Is immobility of rats in the forced swim test ‘behavioral despair’? Physiol Behav 1988; 42: 93–95.

    Article  CAS  PubMed  Google Scholar 

  287. Blanchard RJ, Griebel G, Henrie JA, Blanchard DC . Differentiation of anxiolytic, panicolytic drugs by effects on rat, mouse defense test batteries. Neurosci Biobehav Rev 1997; 21: 783–789.

    Article  CAS  PubMed  Google Scholar 

  288. Fluck E, Hogg S, Jones RB, Bourne R, File SE . Changes in tonic immobility, the GABA–benzodiazepine system in response to handling in the chick. Pharmacol Biochem Behav 1997; 58: 269–274.

    Article  CAS  PubMed  Google Scholar 

  289. Olsen CK, Hogg S, Lapiz MD . Tonic immobility in guinea pigs: a behavioural response for detecting an anxiolytic-like effect? Behav Pharmacol 2002; 13: 261–269.

    Article  CAS  PubMed  Google Scholar 

  290. Armario A, Gavalda A, Marti O . Forced swimming test in rats: effect of desipramine administration, the period of exposure to the test on struggling behavior, swimming, immobility, defecation rate. Eur J Pharmacol 1988; 158: 207–212.

    Article  CAS  PubMed  Google Scholar 

  291. West AP . Neurobehavioral studies of forced swimming: the role of learning, memory in the forced swim test. Prog Neuropsychopharmacol Biol Psychiatry 1990; 14: 863–877.

    Article  CAS  PubMed  Google Scholar 

  292. De Pablo JM, Parra A, Segovia S, Guillamon A . Learned immobility explains the behavior of rats in the forced swimming test. Physiol Behav 1989; 46: 229–237.

    Article  CAS  PubMed  Google Scholar 

  293. Browne RG . Effects of antidepressants, anticholinergics in a mouse ‘behavioral despair’ test. Eur J Pharmacol 1979; 58: 331–334.

    Article  CAS  PubMed  Google Scholar 

  294. West CH, Weiss JM . Effects of antidepressant drugs on rats bred for low activity in the swim test. Pharmacol Biochem Behav 1998; 61: 67–79.

    Article  CAS  PubMed  Google Scholar 

  295. Porsolt RD, Anton G, Blavet N, Jalfre M . Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 1978; 7: 379–391.

    Article  Google Scholar 

  296. Miyakawa T, Yamada M, Duttaroy A, Wess J . Hyperactivity, intact hippocampus-dependent learning in mice lacking the M1 muscarinic acetylcholine receptor. J Neurosci 2001; 1: 5239–5250.

    Article  Google Scholar 

  297. Steru L, Chermat R, Thierry B, Simon P . The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology (Berl) 1985; 5: 367–370.

    Article  Google Scholar 

  298. Porsolt RD, Chermat R, Lenegre A, Avril I, Janvier S, Steru L . Use of the automated tail suspension test for the primary screening of psychotropic agents. Arch Int Pharmacodyn Ther 1987; 88: 11–30.

    Google Scholar 

  299. Steru L, Chermat R, Thierry B, Mico JA, Lenegre A, Steru M et al. The automated tail suspension test: a computerized device which differentiates psychotropic drugs. Prog Neuropsychopharmacol Biol Psychiatry 1987; 11: 659–671.

    Article  CAS  PubMed  Google Scholar 

  300. Bai F, Li X, Clay M, Lindstrom T, Skolnick P . Intra-, interstrain differences in models of ‘behavioral despair’. Pharmacol Biochem Behav 2001; 70: 187–192.

    Article  CAS  PubMed  Google Scholar 

  301. Renard CE, Dailly E, David DJ, Hascoet M, Bourin M . Monoamine metabolism changes following the mouse forced swimming test but not the tail suspension test. Fund Clin Pharmacol 2003; 17: 449–455.

    Article  CAS  Google Scholar 

  302. Mayorga AJ, Lucki I . Limitations on the use of the C57BL/6 mouse in the tail suspension test. Psychopharmacology (Berl) 2001; 155: 110–112.

    Article  CAS  Google Scholar 

  303. Ripoll N, David DJ, Dailly E, Hascoet M, Bourin M . Antidepressant-like effects in various mice strains in the tail suspension test. Behav Brain Res 2003; 143: 193–200.

    Article  CAS  PubMed  Google Scholar 

  304. Liu X, Gershenfeld HK . Genetic differences in the tail-suspension test, its relationship to imipramine response among 11 inbred strains of mice. Biol Psychiatry 2001; 49: 575–581.

    Article  CAS  PubMed  Google Scholar 

  305. Liu X, Gershenfeld HK . An exploratory factor analysis of the tail suspension test in 12 inbred strains of mice, an F2 intercross. Brain Res Bull 2003; 60: 223–231.

    Article  PubMed  Google Scholar 

  306. Jesberger JA, Richardson JS . Brain output dysregulation induced by olfactory bulbectomy: an approximation in the rat of major depressive disorder in humans? Int J Neurosci 1988; 38: 241–265.

    Article  CAS  PubMed  Google Scholar 

  307. Kelly JP, Wrynn AS, Leonard BE . The olfactory bulbectomized rat as a model of depression: an update. Pharmacol Ther 1997; 74: 299–316.

    Article  CAS  PubMed  Google Scholar 

  308. Lumia AR, Teicher MH, Salchli F, Ayers E, Possidente B . Olfactory bulbectomy as a model for agitated hyposerotonergic depression. Brain Res 1992; 587: 181–185.

    Article  CAS  PubMed  Google Scholar 

  309. van Riezen H, Leonard BE . Effects of psychotropic drugs on the behavior, neurochemistry of olfactory bulbectomized rats. Pharmacol Ther 1990; 47: 21–34.

    Article  CAS  PubMed  Google Scholar 

  310. Neckers LM, Zarrow MX, Myers MM, Denenberg VH . Influence of olfactory bulbectomy, the serotonergic system upon intermale aggression, maternal behavior in the mouse. Pharmacol Biochem Behav 1975; 3: 545–550.

    Article  CAS  PubMed  Google Scholar 

  311. Otmakhova NA, Gurevich EV, Katkov YA, Nesterova IV, Bobkova NV . Dissociation of multiple behavioral effects between olfactory bulbectomized C57Bl/6J, DBA/2J mice. Physiol Behav 1992; 52: 441–448.

    Article  CAS  PubMed  Google Scholar 

  312. Gurevich EV, Aleksandrova IA, Otmakhova NA, Katkov YA, Nesterova IV, Bobkova NV . Effects of bulbectomy and subsequent antidepressant treatment on brain 5-HT2 and 5-HT1A receptors in mice. Pharmacol Biochem Behav 1993; 45: 65–70.

    Article  CAS  PubMed  Google Scholar 

  313. Possidente B, Lumia AR, McGinnis MY, Rapp M, McEldowney S . Effects of fluoxetine, olfactory bulbectomy on mouse circadian activity rhythms. Brain Res 1996; 713: 108–113.

    Article  CAS  PubMed  Google Scholar 

  314. Nesterova IV, Gurevich EV, Nesterov VI, Otmakhova NA, Bobkova NV . Bulbectomy-induced loss of raphe neurons is counteracted by antidepressant treatment. Prog Neuropsychopharmacol Biol Psychiatry 1997; 21: 127–140.

    Article  CAS  PubMed  Google Scholar 

  315. Komori T, Yamamoto M, Matsumoto T, Zhang K, Okazaki Y . Effects of imipramine on T cell subsets in olfactory bulbectomized mice. Neuropsychobiology 2002; 46: 194–196.

    Article  CAS  PubMed  Google Scholar 

  316. Cryan JF, McGrath C, Leonard BE, Norman TR . Combining pindolol, paroxetine in an animal model of chronic antidepressant action—can early onset of action be detected? Eur J Pharmacol 1998; 352: 23–28.

    Article  CAS  PubMed  Google Scholar 

  317. Cryan JF, McGrath C, Leonard BE, Norman TR . Onset of the effects of the 5-HT1A antagonist, WAY-100635, alone, and in combination with paroxetine, on olfactory bulbectomy, 8-OH-DPAT-induced changes in the rat. Pharmacol Biochem Behav 1999; 63: 333–338.

    Article  CAS  PubMed  Google Scholar 

  318. Primeaux SD, Holmes PV . Role of aversively motivated behavior in the olfactory bulbectomy syndrome. Physiol Behav 1999; 67: 41–47.

    Article  CAS  PubMed  Google Scholar 

  319. Mar A, Spreekmeester E, Rochford J . Antidepressants preferentially enhance habituation to novelty in the olfactory bulbectomized rat. Psychopharmacology (Berl) 2000; 150: 52–60.

    Article  CAS  Google Scholar 

  320. Zhou D, Grecksch G, Becker A, Frank C, Pilz J, Huether G . Serotonergic hyperinnervation of the frontal cortex in an animal model of depression, the bulbectomized rat. J Neurosci Res 1998; 54: 109–116.

    Article  CAS  PubMed  Google Scholar 

  321. Connor TJ, Song C, Leonard BE, Anisman H, Merali Z . Stressor-induced alterations in serotonergic activity in an animal model of depression. Neuroreport 1999; 10: 523–528.

    Article  CAS  PubMed  Google Scholar 

  322. Watanabe A, Tohyama Y, Nguyen KQ, Hasegawa S, Debonnel G, Diksic M . Regional brain serotonin synthesis is increased in the olfactory bulbectomy rat model of depression: an autoradiographic study. J Neurochem 2003; 85: 469–475.

    Article  CAS  PubMed  Google Scholar 

  323. Ho YJ, Chang YC, Liu TM, Tai MY, Wong CS, Tsai YF . Striatal glutamate release during novelty exposure-induced hyperactivity in olfactory bulbectomized rats. Neurosci Lett 2000; 287: 117–120.

    Article  CAS  PubMed  Google Scholar 

  324. Robichaud M, Beauchemin V, Lavoie N, Dennis T, Debonnel G . Effects of bilateral olfactory bulbectomy on N-methyl-D-aspartate receptor function: autoradiographic, behavioral studies in the rat. Synapse 2001; 42: 95–103.

    Article  CAS  PubMed  Google Scholar 

  325. Earley B, Glennon M, Lally M, Leonard BE, Junien J-L . Autoradiographic distribution of cholinergic muscarinic receptors, serotonin2 receptors in olfactory bulbectoized (OB) rats after chronic treatment with mianserin and desipramine. Hum Psychopharmacol 1994; 9: 397–407.

    Article  CAS  Google Scholar 

  326. Hozumi S, Nakagawasai O, Tan-No K, Niijima F, Yamadera F, Murata A et al. Characteristics of changes in cholinergic function, impairment of learning, memory-related behavior induced by olfactory bulbectomy. Behav Brain Res 2003; 138: 9–15.

    Article  CAS  PubMed  Google Scholar 

  327. Holmes PV . Olfactory bulbectomy increases prepro-enkephalin mRNA levels in the ventral striatum in rats. Neuropeptides 1999; 33: 206–211.

    Article  CAS  PubMed  Google Scholar 

  328. Gottesfeld Z, Garcia CJ, Lingham RB, Chronister RB . Prenatal ethanol exposure impairs lesion-induced plasticity in a dopaminergic synapse after maturity. Neuroscience 1989; 29: 715–723.

    Article  CAS  PubMed  Google Scholar 

  329. Dennis T, Beauchemin V, Lavoie N . Differential effects of olfactory bulbectomy on GABAA, GABAB receptors in the rat brain. Pharmacol Biochem Behav 1993; 46: 77–82.

    Article  CAS  PubMed  Google Scholar 

  330. Slotkin TA, Miller DB, Fumagalli F, McCook EC, Zhang J, Bissette G et al. Modeling geriatric depression in animals: biochemical, behavioral effects of olfactory bulbectomy in young versus aged rats. J Pharmacol Exp Ther 1999; 289: 334–345.

    CAS  PubMed  Google Scholar 

  331. McNish KA, Davis M . Olfactory bulbectomy enhances sensitization of the acoustic startle reflex produced by acute or repeated stress. Behav Neurosci 1997; 111: 80–91.

    Article  CAS  PubMed  Google Scholar 

  332. van Rijzingen IM, Gispen WH, Spruijt BM . Olfactory bulbectomy temporarily impairs Morris maze performance: an ACTH(4-9) analog accellerates return of function. Physiol Behav 1995; 58: 147–152.

    Article  CAS  PubMed  Google Scholar 

  333. Marcilhac A, Anglade G, Hery F, Siaud P . Olfactory bulbectomy increases vasopressin, but not corticotropin-releasing hormone, content in the external layer of the median eminence of male rats. Neurosci Lett 1999; 262: 89–92.

    Article  CAS  PubMed  Google Scholar 

  334. Marcilhac A, Anglade G, Hery F, Siaud P . Effects of bilateral olfactory bulbectomy on the anterior pituitary corticotropic cell activity in male rats. Horm Metab Res 1999; 31: 399–401.

    Article  CAS  PubMed  Google Scholar 

  335. Marcilhac A, Faudon M, Anglade G, Hery F, Siaud P . An investigation of serotonergic involvement in the regulation of ACTH, corticosterone in the olfactory bulbectomized rat. Pharmacol Biochem Behav 1999; 63: 599–605.

    Article  CAS  PubMed  Google Scholar 

  336. Katkov YA, Otmakhova NA, Gurevich EV, Nesterova IV, Bobkova NV . Antidepressants suppress bulbectomy-induced augmentation of voluntary alcohol consumption in C57B1/6j but not in DBA/2j mice. Physiol Behav 1994; 56: 501–509.

    Article  CAS  PubMed  Google Scholar 

  337. Uzunova V, Ceci M, Kohler C, Uzunov DP, Wrynn AS . Region-specific dysregulation of allopregnanolone brain content in the olfactory bulbectomized rat model of depression. Brain Res 2003; 976: 1–8.

    Article  CAS  PubMed  Google Scholar 

  338. Sieck MH, Baumbach HD . Differential effects of peripheral, central anosmia producing techniques on spontaneous behavior patterns. Physiol Behav 1974; 13: 407–425.

    Article  CAS  PubMed  Google Scholar 

  339. van Riezen H, Schnieden H, Wren AF . Olfactory bulb ablation in the rat: behavioural changes, their reversal by antidepressant drugs. Br J Pharmacol 1977; 60: 521–528.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  340. Grecksch G, Zhou D, Franke C, Schroder U, Sabel B, Becker A et al. Influence of olfactory bulbectomy, subsequent imipramine treatment on 5-hydroxytryptaminergic presynapses in the rat frontal cortex: behavioural correlates. Br J Pharmacol 1997; 122: 1725–1731.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  341. Norrholm SD, Ouimet CC . Altered dendritic spine density in animal models of depression, in response to antidepressant treatment. Synapse 2001; 42: 151–163.

    Article  CAS  PubMed  Google Scholar 

  342. Overmier JB, Seligman ME . Effects of inescapable shock upon subsequent escape, avoidance responding. J Comp Physiol Psychol 1967; 63: 28–33.

    Article  CAS  PubMed  Google Scholar 

  343. Seligman ME, Maier SF . Failure to escape traumatic shock. J Exp Psychol 1967; 74: 1–9.

    Article  CAS  PubMed  Google Scholar 

  344. Seligman ME, Beagley G . Learned helplessness in the rat. J Comp Physiol Psychol 1975; 88: 534–541.

    Article  CAS  PubMed  Google Scholar 

  345. Anisman H, Irwin J, Sklar LS . Deficits of escape performance following catecholamine depletion: implications for behavioral deficits induced by uncontrollable stress. Psychopharmacology (Berl) 1979; 64: 163–170.

    Article  CAS  Google Scholar 

  346. Anisman H, DeCatanzaro D, Remington G . Escape performance following exposure to inescapable shock: deficits in motor response maintenance. J Exp Psychol Anim Behav Process 1978; 4: 197–218.

    Article  Google Scholar 

  347. Leshner AI, Remler H, Biegon A, Samuel D . Desmethylimipramine (DMI) counteracts learned helplessness in rats. Psychopharmacology (Berl) 1979; 66: 207–208.

    Article  CAS  Google Scholar 

  348. Sherman AD, Petty F . Additivity of neurochemical changes in learned helplessness, imipramine. Behav Neural Biol 1982; 35: 344–353.

    Article  CAS  PubMed  Google Scholar 

  349. Martin P, Soubrie P, Puech AJ . Reversal of helpless behavior by serotonin uptake blockers in rats. Psychopharmacology (Berl) 1990; 101: 403–407.

    Article  CAS  Google Scholar 

  350. Weiss JM, Kilts CD . Animal models of depression, schizophrenia. In: Nemeroff, CB, Schatzberg AF (eds). Textbook of Psychopharmacology, 2nd edn American Psychiatric Press: Washington, DC, 1998; 88–123.

    Google Scholar 

  351. Drugan RC, Skolnick P, Paul SM, Crawley JN . A pretest procedure reliably predicts performance in two animal models of inescapable stress. Pharmacol Biochem Behav 1989; 33: 649–654.

    Article  CAS  PubMed  Google Scholar 

  352. Vollmayr B, Henn FA . Learned helplessness in the rat: improvements in validity, reliability. Brain Res Brain Res Protoc 2001; 8: 1–7.

    Article  CAS  PubMed  Google Scholar 

  353. Shanks N, Anisman H . Escape deficits induced by uncontrollable foot-shock in recombinant inbred strains of mice. Pharmacol Biochem Behav 1993; 46: 511–517.

    Article  CAS  PubMed  Google Scholar 

  354. Shanks N, Anisman H . Strain-specific effects of antidepressants on escape deficits induced by inescapable shock. Psychopharmacology (Berl) 1989; 99: 122–128.

    Article  CAS  Google Scholar 

  355. Shanks N, Anisman H . Stressor-provoked behavioral changes in six strains of mice. Behav Neurosci 1988; 102: 894–905.

    Article  CAS  PubMed  Google Scholar 

  356. Mogil JS, Wilson SG, Bon K, Lee SE, Chung K, Raber P et al. Heritability of nociception I: responses of 11 inbred mouse strains on 12 measures of nociception. Pain 1999; 80: 67–82.

    Article  CAS  PubMed  Google Scholar 

  357. MacQueen GM, Ramakrishnan K, Croll SD, Siuciak JA, Yu G, Young LT et al. Performance of heterozygous brain-derived neurotrophic factor knockout mice on behavioral analogues of anxiety, nociception, and depression. Behav Neurosci 2001; 115: 1145–1153.

    Article  CAS  PubMed  Google Scholar 

  358. Barr AM, Phillips AG . Withdrawal following repeated exposure to D-amphetamine decreases responding for a sucrose solution as measured by a progressive ratio schedule of reinforcement. Psychopharmacology (Berl) 1999; 141: 99–106.

    Article  CAS  Google Scholar 

  359. Lynch MA, Leonard BE . Changes in brain gamma-aminobutyric acid concentrations following acute, chronic amphetamine administration, during post amphetamine depression. Biochem Pharmacol 1978; 27: 1853–1855.

    Article  CAS  PubMed  Google Scholar 

  360. Barr AM, Fiorino DF, Phillips AG . Effects of withdrawal from an escalating dose schedule of D-amphetamine on sexual behavior in the male rat. Pharmacol Biochem Behav 1999; 64: 597–604.

    Article  CAS  PubMed  Google Scholar 

  361. Barr AM, Zis AP, Phillips AG . Repeated electroconvulsive shock attenuates the depressive-like effects of D-amphetamine withdrawal on brain reward function in rats. Psychopharmacology (Berl) 2002; 159: 196–202.

    Article  CAS  Google Scholar 

  362. Ikeda K, Moss SJ, Fowler SC, Niki H . Comparison of two intracranial self-stimulation (ICSS) paradigms in C57BL/6 mice: head-dipping and place-learning. Behav Brain Res 2001; 126: 49–56.

    Article  CAS  PubMed  Google Scholar 

  363. Willner P, Muscat R, Papp M . An animal model of anhedonia. Clin Neuropharmacol 1992; 15(Suppl 1, Part A): 550A–551A.

    Article  PubMed  Google Scholar 

  364. Willner P, Muscat R, Papp M . Chronic mild stress-induced anhedonia: a realistic animal model of depression. Neurosci Biobehav Rev 1992; 16: 525–534.

    Article  CAS  PubMed  Google Scholar 

  365. Willner P . Validity, reliability, utility of the chronic mild stress model of depression: a 10-year review, evaluation. Psychopharmacology (Berl) 1997; 134: 319–329.

    Article  CAS  Google Scholar 

  366. Moreau JL, Jenck F, Martin JR, Mortas P, Haefely WE . Antidepressant treatment prevents chronic unpredictable mild stress-induced anhedonia as assessed by ventral tegmentum self-stimulation behavior in rats. Eur Neuropsychopharmacol 1992; 2: 43–49.

    Article  CAS  PubMed  Google Scholar 

  367. Matthews K, Forbes N, Reid IC . Sucrose consumption as an hedonic measure following chronic unpredictable mild stress. Physiol Behav 1995; 57: 241–248.

    Article  CAS  PubMed  Google Scholar 

  368. Forbes NF, Stewart CA, Matthews K, Reid IC . Chronic mild stress, sucrose consumption: validity as a model of depression. Physiol Behav 1996; 60: 1481–1484.

    Article  CAS  PubMed  Google Scholar 

  369. Reid I, Forbes N, Stewart C, Matthews K . Chronic mild stress, depressive disorder: a useful new model? Psychopharmacology (Berl) 1997; 134: 365–367, discussion 371–377.

    Article  CAS  Google Scholar 

  370. Hatcher JP, Bell DJ, Reed TJ, Hagan JJ . Chronic mild stress-induced reductions in saccharin intake depend upon feeding status. J Psychopharmacol 1997; 11: 331–338.

    Article  CAS  PubMed  Google Scholar 

  371. Harris RB, Zhou J, Youngblood BD, Smagin GN, Ryan DH . Failure to change exploration or saccharin preference in rats exposed to chronic mild stress. Physiol Behav 1997; 63: 91–100.

    Article  CAS  PubMed  Google Scholar 

  372. Nielsen CK, Arnt J, Sanchez C . Intracranial self-stimulation, sucrose intake differ as hedonic measures following chronic mild stress: interstrain, interindividual differences. Behav Brain Res 2000; 107: 21–33.

    Article  CAS  PubMed  Google Scholar 

  373. Bielajew C, Konkle AT, Merali Z . The effects of chronic mild stress on male Sprague–Dawley, Long Evans rats: I. Biochemical, physiological analyses. Behav Brain Res 2002; 136: 583–592.

    Article  CAS  PubMed  Google Scholar 

  374. Harkin A, Houlihan DD, Kelly JP . Reduction in preference for saccharin by repeated unpredictable stress in mice, its prevention by imipramine. J Psychopharmacol 2002; 16: 115–123.

    Article  CAS  PubMed  Google Scholar 

  375. Ducottet C, Griebel G, Belzung C . Effects of the selective nonpeptide corticotropin-releasing factor receptor 1 antagonist antalarmin in the chronic mild stress model of depression in mice. Prog Neuropsychopharmacol Biol Psychiatry 2003; 27: 625–631.

    Article  CAS  PubMed  Google Scholar 

  376. Griebel G, Simiand J, Serradeil-Le Gal C, Wagnon J, Pascal M, Scatton B et al. Anxiolytic-, antidepressant-like effects of the non-peptide vasopressin V1b receptor antagonist, SSR149415, suggest an innovative approach for the treatment of stress-related disorders. Proc Natl Acad Sci USA 2002; 99: 6370–6375.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  377. Griebel G, Simiand J, Steinberg R, Jung M, Gully D, Roger P et al. 4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4- methylphenyl)ethyl]5-methyl-N-(2-propynyl)-1, 3-thiazol-2-amine hydrochloride (SSR125543A), a potent and selective corticotrophin-releasing factor(1) receptor antagonist. II. Characterization in rodent models of stress-related disorders. J Pharmacol Exp Ther 2002; 301: 333–345.

    Article  CAS  PubMed  Google Scholar 

  378. Porsolt RD, Bertin A, Jalfre M . Behavioural despair' in rats, mice: strain differences, the effects of imipramine. Eur J Pharmacol 1978; 51: 291–294.

    Article  CAS  PubMed  Google Scholar 

  379. Russig H, Pezze MA, Nanz-Bahr NI, Pryce CR, Feldon J, Murphy CA et al. Amphetamine withdrawal does not produce a depressive-like state in rats as measured by three behavioral tests. Behav Pharmacol 2003; 14: 1–18.

    Article  CAS  PubMed  Google Scholar 

  380. Gross C, Santarelli L, Brunner D, Zhuang X, Hen R . Altered fear circuits in 5-HT(1A) receptor KO mice. Biol Psychiatry 2000; 48: 1157–1163.

    Article  CAS  PubMed  Google Scholar 

  381. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 2003; 301: 805–809.

    Article  CAS  PubMed  Google Scholar 

  382. Koenig JI, Kirkpatrick B, Lee P . Glucocorticoid hormones, early brain development in schizophrenia. Neuropsychopharmacology 2002; 27: 309–318.

    Article  CAS  PubMed  Google Scholar 

  383. Vogel G, Neill D, Hagler M, Kors D . A new animal model of endogenous depression: a summary of present findings. Neurosci Biobehav Rev 1990; 14: 85–91.

    Article  CAS  PubMed  Google Scholar 

  384. Velazquez-Moctezuma J, Diaz Ruiz O . Neonatal treatment with clomipramine increased immobility in the forced swim test: an attribute of animal models of depression. Pharmacol Biochem Behav 1992; 42: 737–739.

    Article  CAS  PubMed  Google Scholar 

  385. Hansen HH, Sanchez C, Meier E . Neonatal administration of the selective serotonin reuptake inhibitor Lu 10-134-C increases forced swimming-induced immobility in adult rats: a putative animal model of depression? J Pharmacol Exp Ther 1997; 283: 1333–1341.

    CAS  PubMed  Google Scholar 

  386. Prathiba J, Kumar KB, Karanth KS . Hyperactivity of hypothalamic pituitary axis in neonatal clomipramine model of depression. J Neural Transm 1998; 105: 1335–1339.

    Article  CAS  PubMed  Google Scholar 

  387. Schmidt M, Oitzl MS, Levine S, de Kloet ER . The HPA system during the postnatal development of CD1 mice, the effects of maternal deprivation. Brain Res Dev Brain Res 2002; 139: 39–49.

    Article  CAS  PubMed  Google Scholar 

  388. Matthews K, Robbins TW . Early experience as a determinant of adult behavioural responses to reward: the effects of repeated maternal separation in the rat. Neurosci Biobehav Rev 2003; 27: 45–55.

    Article  PubMed  Google Scholar 

  389. Pattij T, Broersen LM, van der Linde J, Groenink L, van der Gugten J, Maes RA et al. Operant leaning and differential-reinforcement-of-low-rate 36-s responding in 5-HT1A and 5-HT1B receptor knockout mice. Behav Brain Res 2003; 141: 137–145.

    Article  CAS  PubMed  Google Scholar 

  390. Seiden LS, Dahms JL, Shaughnessy RA . Behavioral screen for antidepressants: the effects of drugs, electroconvulsive shock on performance under a differential-reinforcement-of-low-rate schedule. Psychopharmacology (Berl) 1985; 86: 55–60.

    Article  CAS  Google Scholar 

  391. Mitchell PJ, Redfern PH . Potentiation of the time-dependent, antidepressant-induced changes in the agonistic behaviour of resident rats by the 5-HT1A receptor antagonist, WAY-100635. Behav Pharmacol 1997; 8: 585–606.

    Article  CAS  PubMed  Google Scholar 

  392. Yirmiya R, Pollak Y, Barak O, Avitsur R, Ovadia H, Bette M et al. Effects of antidepressant drugs on the behavioral, physiological responses to lipopolysaccharide (LPS) in rodents. Neuropsychopharmacology 2001; 24: 531–544.

    Article  CAS  PubMed  Google Scholar 

  393. Shen Y, Connor TJ, Nolan Y, Kelly JP, Leonard BE . Differential effect of chronic antidepressant treatments on lipopolysaccharide-induced depressive-like behavioural symptoms in the rat. Life Sci 1999; 65: 1773–1786.

    Article  CAS  PubMed  Google Scholar 

  394. Dunn AJ, Swiergiel AH . The reductions in sweetened milk intake induced by interleukin-1, endotoxin are not prevented by chronic antidepressant treatment. Neuroimmunomodulation 2001; 9: 163–169.

    Article  CAS  PubMed  Google Scholar 

  395. Edwards E, King JA, Fray J . Hypertension, insulin resistant models have divergent propensities to learned helpless behavior in rodents. Am J Hypertens 2000; 13: 659–665.

    Article  CAS  PubMed  Google Scholar 

  396. Kohen R, Neumaier JF, Hamblin MW, Edwards E . Congenitally learned helpless rats show abnormalities in intracellular signaling. Biol Psychiatry 2003; 53: 520–529.

    Article  PubMed  Google Scholar 

  397. Scott PA, Cierpial MA, Kilts CD, Weiss JM . Susceptibility, resistance of rats to stress-induced decreases in swim-test activity: a selective breeding study. Brain Res 1996; 725: 217–230.

    Article  CAS  PubMed  Google Scholar 

  398. Overstreet DH, Russell RW, Hay DA, Crocker AD . Selective breeding for increased cholinergic function: biometrical genetic analysis of muscarinic responses. Neuropsychopharmacology 1992; 7: 197–204.

    CAS  PubMed  Google Scholar 

  399. Yadid G, Nakash R, Deri I, Tamar G, Kinor N, Gispan I et al. Elucidation of the neurobiology of depression: insights from a novel genetic animal model. Prog Neurobiol 2000; 62: 353–378.

    Article  CAS  PubMed  Google Scholar 

  400. Overstreet DH, Commissaris RC, De La Garza II R, File SE, Knapp DJ, Seiden LS . Involvement of 5-HT1A receptors in animal tests of anxiety, depression: evidence from genetic models. Stress 2003; 6: 101–110.

    Article  CAS  PubMed  Google Scholar 

  401. Knapp DJ, Sim-Selley LJ, Breese GR, Overstreet DH . Selective breeding of 5-HT(1A) receptor-mediated responses: application to emotion and receptor action. Pharmacol Biochem Behav 2000; 67: 701–708.

    Article  CAS  PubMed  Google Scholar 

  402. Suaudeau C, Rinaldi D, Lepicard E, Venault P, Crusio WE, Costentin J et al. Divergent levels of anxiety in mice selected for differences in sensitivity to a convulsant agent. Physiol Behav 2000; 71: 517–523.

    Article  CAS  PubMed  Google Scholar 

  403. Do-Rego JC, Suaudeau C, Chapouthier G, Costentin J . Mouse lines differing in sensitivity to beta-CCM differ in tasks used for testing antidepressants. Pharmacol Biochem Behav 2002; 72: 411–416.

    Article  CAS  PubMed  Google Scholar 

  404. Morgan TJ, Garland Jr T, Carter PA . Ontogenies in mice selected for high voluntary wheel-running activity. I. Mean ontogenies. Evol Int J Org Evol 2003; 57: 646–657.

    Article  Google Scholar 

  405. Tarantino LM, Gould TJ, Druhan JP, Bucan M . Behavior, mutagenesis screens: the importance of baseline analysis of inbred strains. Mamm Genome 2000; 11: 555–564.

    Article  CAS  PubMed  Google Scholar 

  406. Naudon L, El Yacoubi M, Vaugeois JM, Leroux-Nicollet I, Costentin J . A chronic treatment with fluoxetine decreases 5-HT(1A) receptors labeling in mice selected as a genetic model of helplessness. Brain Res 2002; 936: 68–75.

    Article  CAS  PubMed  Google Scholar 

  407. Gross C, Zhuang X, Stark K, Ramboz S, Oosting R, Kirby L et al. Serotonin1A receptor acts during development to establish normal anxiety-like behaviour in the adult. Nature 2002; 416: 396–400.

    Article  CAS  PubMed  Google Scholar 

  408. Cryan JF, Hirsch BR, Jin S-H, Lucki I, Thomas SA . Reduced sensitivity to the antidepressant-like effects of SSRIs in dopamine-Beta -hydroxylase deficient mice. Program No. 665.9 2001 Abstract Viewer/Itinerary Planner. Society for Neuroscience: Washington, DC, 2001 (online).

    Google Scholar 

  409. Meaney MJ . Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu Rev Neurosci 2001; 24: 1161–1192.

    Article  CAS  PubMed  Google Scholar 

  410. Stohr T, Schulte Wermeling D, Szuran T, Pliska V, Domeney A, Welzl H et al. Differential effects of prenatal stress in two inbred strains of rats. Pharmacol Biochem Behav 1998; 59: 799–805.

    Article  CAS  PubMed  Google Scholar 

  411. Ladd CO, Owens MJ, Nemeroff CB . Persistent changes in corticotropin-releasing factor neuronal systems induced by maternal deprivation. Endocrinology 1996; 137: 1212–1218.

    Article  CAS  PubMed  Google Scholar 

  412. Pryce CR, Feldon J . Long-term neurobehavioural impact of the postnatal environment in rats: manipulations, effects, mediating mechanisms. Neurosci Biobehav Rev 2003; 27: 57–71.

    Article  PubMed  Google Scholar 

  413. Francis DD, Champagne FA, Liu D, Meaney MJ . Maternal care, gene expression, and the development of individual differences in stress reactivity. Ann NY Acad Sci 1999; 896: 66–84.

    Article  CAS  PubMed  Google Scholar 

  414. Francis D, Diorio J, Liu D, Meaney MJ . Nongenomic transmission across generations of maternal behaviour and stress responses in the rat. Science 1999; 286: 1155–1158.

    Article  CAS  PubMed  Google Scholar 

  415. Francis DD, Szegda K, Campbell G, Martin WD, Insel TR . Epigenetic sources of behavioral differences in mice. Nat Neurosci 2003; 6: 445–446.

    Article  CAS  PubMed  Google Scholar 

  416. Crabbe JC, Phillips TJ . Mother nature meets mother nurture. Nat Neurosci 2003; 6: 440–442.

    Article  CAS  PubMed  Google Scholar 

  417. Pfaff D . Precision in mouse behavior genetics. Proc Natl Acad Sci USA 2001; 98: 5957–5960.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  418. Zambrowicz BP, Sands AT . Knockouts model the 100 best-selling drugs—will they model the next 100? Nat Rev Drug Discov 2003; 2: 38–51.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

JFC is supported by National Institutes of Mental Health/National Institute on Drug Abuse Grant U01 MH69062. CM is a Doctoral students affiliated with the Laboratoire de Neuroscience Cognitives, CNRS UMR 5106, Université de Bordeaux 1, Avenue des Facultés, Talence cedex 33405, France. We thank Dr Conrad Gentsch, Novartis Institutes for Biomedical Sciences, Basel for a critical reading of the manuscript. We also acknowledge Dr Irwin Lucki, University of Pennsylvania and Dr Athina Markou, The Scripps Research Institute for many fruitful discussions on depression models.

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Cryan, J., Mombereau, C. In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice. Mol Psychiatry 9, 326–357 (2004). https://doi.org/10.1038/sj.mp.4001457

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