Skip to main content

Advertisement

SpringerLink
Log in

Repeated social defeat and the rewarding effects of cocaine in adult and adolescent mice: dopamine transcription factors, proBDNF signaling pathways, and the TrkB receptor in the mesolimbic system

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Repeated social defeat (RSD) increases the rewarding effects of cocaine in adolescent and adult rodents.

Objective

The aim of the present study was to compare the long-term effects of RSD on the conditioned rewarding effects of cocaine and levels of the transcription factors Pitx3 and Nurr1 in the ventral tegmental area (VTA), the dopamine transporter (DAT), the D2 dopamine receptor (D2DR) and precursor of brain-derived neurotrophic factor (proBDNF) signaling pathways, and the tropomyosin-related kinase B (TrkB) receptor in the nucleus accumbens (NAc) in adult and adolescent mice.

Methods

Male adolescent and young adult OF1 mice were exposed to four episodes of social defeat and were conditioned 3 weeks later with 1 mg/kg of cocaine. In a second set of mice, the expressions of the abovementioned dopaminergic and proBDNF and TrkB receptor were measured in VTA and NAc, respectively.

Results

Adolescent mice experienced social defeats less intensely than their adult counterparts and produced lower levels of corticosterone. However, both adult and adolescent defeated mice developed conditioned place preference for the compartment associated with this low dose of cocaine. Furthermore, only adolescent defeated mice displayed diminished levels of the transcription factors Pitx3 in the VTA, without changes in the expression of DAT and D2DR in the NAc. In addition, stressed adult mice showed a decreased expression of proBDNF and the TrkB receptor, while stressed adolescent mice exhibited increased expression of latter without changes in the former.

Conclusion

Our findings suggest that dopaminergic pathways and proBDNF signaling and TrkB receptors play different roles in social defeat-stressed mice exposed to cocaine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Aloyz R, Fawcett JP, Kaplan DR, Murphy RA, Miller FD (1999) Activity-dependent activation of TrkB neurotrophin receptors in the adult CNS. Learn Mem 6:216–231

    CAS  PubMed  PubMed Central  Google Scholar 

  • Altar CA, Cai N, Bliven T, Juhasz M, Conner JM, Acheson AL, Lindsay RM, Wiegand SJ (1997) Anterograde transport of brain-derived neurotrophic factor and its role in the brain. Nature 389:856–860

    Article  CAS  PubMed  Google Scholar 

  • Arenas MC, Daza-Losada M, Vidal-Infer A, Aguilar MA, Miñarro J, Rodríguez-Arias M (2014) Capacity of novelty-induced locomotor activity and the hole-board test to predict sensitivity to the conditioned rewarding effects of cocaine. Physiol Behav 133:152–160. doi:10.1016/j.physbeh.2014.05.028

    Article  CAS  PubMed  Google Scholar 

  • Autry AE (2016) Neurobiology of chronic social defeat stress: role of brain-derived neurotrophic factor signaling in the nucleus accumbens. Biol Psychiatry 80:e39–e40. doi:10.1016/j.biopsych.2016.07.006

    Article  PubMed  Google Scholar 

  • Autry AE, Monteggia LM (2012) Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol Rev 64:238–258 10.1124/pr.111.005108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Badanich KA, Adler KJ, Kirstein CL (2006) Adolescents differ from adults in cocaine conditioned place preference and cocaine-induced dopamine in the nucleus accumbens septi. Eur J Pharmacol 550(1–3):95–106. doi:10.1016/j.ejphar.2006.08.034

    Article  CAS  PubMed  Google Scholar 

  • Belujon P, Grace AA (2011) Hippocampus, amygdala, and stress: interacting systems that affect susceptibility to addiction. Ann N Y Acad Sci 1216:114–121. doi:10.1111/j.1749-6632.2010.05896.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berton O, McClung CA, Dileone RJ, Krishnan V, Renthal W, Russo SJ, Graham D, Tsankova NM, Bolanos CA, Rios M, Monteggia LM, Self DW, Nestler EJ (2006) Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science 311:864–868

    Article  CAS  PubMed  Google Scholar 

  • Bissonette GB, Roesch MR (2015) Development and function of the midbrain dopamine system: what we know and what we need to. Genes Brain Behav 15(1):62–73. doi:10.1111/gbb.12257

    Article  PubMed  PubMed Central  Google Scholar 

  • Bromberg-Martin ES, Matsumoto M, Hikosaka O (2010) Dopamine in motivational control: rewarding, aversive, and alerting. Neuron 68:815–834. doi:10.1016/j.neuron.2010.11.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burke AR, DeBold JF, Miczek KA (2016) CRF type 1 receptor antagonism in ventral tegmental area of adolescent rats during social defeat: prevention of escalated cocaine self-administration in adulthood and behavioral adaptations during adolescence. Psychopharmacology 233(14):2727–2736. doi:10.1007/s00213-016-4336-4

    Article  CAS  PubMed  Google Scholar 

  • Burke AR, Miczek KA (2014) Stress in adolescence and drugs of abuse in rodent models: role of dopamine, CRF, and HPA axis. Psychopharmacology 231(8):1557–1580. doi:10.1007/s00213-013-3369-1

    Article  CAS  PubMed  Google Scholar 

  • Burke AR, Miczek KA (2015) Escalation of cocaine self-administration in adulthood after social defeat of adolescent rats: role of social experience and adaptive coping behavior. Psychopharmacology 232(16):3067–3079. doi:10.1007/s00213-015-3947-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burke AR, Renner KJ, Forster GL, Watt MJ (2010) Adolescent social defeat alters neural, endocrine and behavioral responses to amphetamine in adult male rats. Brain Res 1352:147–156. doi:10.1016/j.brainres.2010.06.062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burke AR, Watt MJ, Forster GL (2011) Adolescent social defeat increases adult amphetamine conditioned place preference and alters D2 dopamine receptor expression. Neuroscience 197:269–279. doi:10.1016/j.neuroscience.2011.09.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caprioli D, Celentano M, Paolone G, Badiani A (2007) Modeling the role of environment in addiction. Prog Neuro-Psychopharmacol Biol Psychiatry 31(8):1639–1653. doi:10.1016/j.pnpbp.2007.08.029

    Article  Google Scholar 

  • Covington HE 3rd, Miczek KA (2005) Intense cocaine self-administration after episodic social defeat stress, but not after aggressive behavior: dissociation from corticosterone activation. Psychopharmacology 183(3):331–340. doi:10.1007/s00213-005-0190-5

    Article  CAS  PubMed  Google Scholar 

  • Covington HE 3rd, Tropea TF, Rajadhyaksha AM, Kosofsky BE, Miczek KA (2008) NMDA receptors in the rat VTA: a critical site for social stress to intensify cocaine taking. Psychopharmacology 197(2):203–216. doi:10.1007/s00213-007-1024-4

    Article  CAS  PubMed  Google Scholar 

  • Cruz FC, Marin MT, Leao RM, Planeta CS (2012) Stress-induced cross-sensitization to amphetamine is related to changes in the dopaminergic system. J Neural Transm 119:415–424. doi:10.1007/s00702-011-0720-8

    Article  CAS  PubMed  Google Scholar 

  • Deroche V, Marinelli M, Maccari S, Le Moal M, Simon H, Piazza PV (1995) Stress-induced sensitization and glucocorticoids. I. Sensitization of dopamine-dependent locomotor effects of amphetamine and morphine depends on stress-induced corticosterone secretion. J Neurosci 15(11):7181–7188. doi:10.1016/0006-8993(93)90526-s

    CAS  PubMed  Google Scholar 

  • Doan SN, Dich N, Evans GW (2014) Childhood cumulative risk and later allostatic load: mediating role of substance use. Health Psychol 33(11):1402–1409. doi:10.1037/a0034790

    Article  PubMed  Google Scholar 

  • Feder A, Nestler EJ, Charney DS (2009) Psychobiology and molecular genetics of resilience. Nat Rev Neurosci 10:446–457. doi:10.1038/nrn2649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fitzgerald LW, Ortiz J, Hamedani AG, Nestler EJ (1996) Drugs of abuse and stress increase the expression of GluR1 and NMDAR1 glutamate receptor subunits in the rat ventral tegmental area: common adaptations among cross-sensitizing agents. J Neurosci 16:274–282

    CAS  PubMed  Google Scholar 

  • Frankin KBJ, Paxinos G (2008) The mouse brain in stereotaxic coordinates. Academic Press, San Diego, CA

  • Garcia-Keller C, Martinez SA, Esparza MA, Bollati F, Kalivas PW, Cancela LM (2013) Cross-sensitization between cocaine and acute restraint stress is associated with sensitized dopamine but not glutamate release in the nucleus accumbens. Eur J Neurosci 37(6):982–995. doi:10.1111/ejn.12121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • García-Pardo MP, Blanco-Gandía MC, Valiente-Lluch M, Rodríguez-Arias M, Miñarro J, Aguilar MA (2015) Long-term effects of repeated social stress on the conditioned place preference induced by MDMA in mice. Prog Neuro-Psychopharmacol Biol Psychiatry 63:98–109. doi:10.1016/j.pnpbp.2015.06.006

    Article  Google Scholar 

  • García-Pardo MP, Rodríguez-Arias M, Maldonado C, Manzanedo C, Miñarro J, Aguilar MA (2014) Effects of acute social stress on the conditioned place preference induced by MDMA in adolescent and adult mice. Behav Pharmacol 25(5–6):532–546. doi:10.1097/FBP.0000000000000065

    PubMed  Google Scholar 

  • García-Pérez D, Núñez C, Laorden ML, Milanés MV (2016) Regulation of dopaminergic markers expression in response to acute and chronic morphine and to morphine withdrawal. Addict Biol 21:374–386. doi:10.1111/adb.12209

    Article  PubMed  Google Scholar 

  • Gerra G, Somaini L, Manfredini M, Raggi MA, Saracino MA, Amore M, Leonardi C, Cortese E, Donnini C (2014) Dysregulated responses to emotions among abstinent heroin users: correlation with childhood neglect and addiction severity. Prog Neuro-Psychopharmacol Biol Psychiatry 48:220–228. doi:10.1016/j.pnpbp.2013.10.011

    Article  CAS  Google Scholar 

  • Goldman L, Coover GO, Levine S (1973) Bidirectional effects of reinforcement shifts on pituitary adrenal activity. Physiol Behav 10(2):209–214. doi:10.1016/0031-9384(73)90299-0

    Article  CAS  PubMed  Google Scholar 

  • Han X, Albrechet-Souza L, Doyle MR, Shimamoto A, DeBold JF, Miczek KA (2015) Social stress and escalated drug self-administration in mice II. Cocaine and dopamine in the nucleus accumbens. Psychopharmacology 232(6):1003–1010. doi:10.1007/s00213-014-3734-8

    Article  CAS  PubMed  Google Scholar 

  • Haney M, Maccari S, Le Moal M, Simon H, Piazza PV (1995) Social stress increases the acquisition of cocaine self-administration in male and female rats. Brain Res 698(1–2):46–52. doi:10.1016/0006-8993(95)00788-r

    Article  CAS  PubMed  Google Scholar 

  • Jacobs FM, van Erp S, van der Linden AJ, von Oerthel L, Burbach JP, Smidt MP (2009) Pitx3 potentiates Nurr1 in dopamine neuron terminal differentiation through release of SMRT-mediated repression. Development 136:531–540. doi:10.1242/dev.029769

    Article  CAS  PubMed  Google Scholar 

  • Kadkhodaei B, Ito T, Joodmardi E, Mattsson B, Rouillard C, Carta M, Muramatsu S, Sumi-Ichinose C, Nomura T, Metzger D, Chambon P, Lindqvist E, Larsson NG, Olson L, Björklund A, Ichinose H, Perlmann T (2009) Nurr1 is required for maintenance of maturing and adult midbrain dopamine neurons. J Neurosci 29:15923–15932. doi:10.1523/JNEUROSCI.3910-09.2009

    Article  CAS  PubMed  Google Scholar 

  • Klein ZA, Romeo RD (2013) Changes in hypothalamic-pituitary-adrenal stress responsiveness before and after puberty in rats. Horm Behav 64:357–363. doi:10.1016/j.yhbeh.2013.01.012

    Article  CAS  PubMed  Google Scholar 

  • Koob GF (2010) The role of CRF and CRF-related peptides in the dark side of addiction. Brain Res 1314:3–14. doi:10.1016/j.brainres.2009.11.008

    Article  CAS  PubMed  Google Scholar 

  • Krishnan V, Han MH, Graham DL, Berton O, Renthal W, Russo SJ, Laplant Q, Graham A, Lutter M, Lagace DC, Ghose S, Reister R, Tannous P, Green TA, Neve RL, Chakravarty S, Kumar A, Eisch AJ, Self DW, Lee FS, Tamminga CA, Cooper DC, Gershenfeld HK, Nestler EJ (2007) Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell 131:391–404. doi:10.1016/j.cell.2007.09.018

    Article  CAS  PubMed  Google Scholar 

  • Laviola G, Pascucci T, Pieretti S (2001) Striatal dopamine sensitization to D-amphetamine in periadolescent but not in adult rats. Pharmacol Biochem Behav 68(1):115–124. doi:10.1016/S0091-3057(00)00430-5

    Article  CAS  PubMed  Google Scholar 

  • Le Moal M (2009) Drug abuse: vulnerability and transition to addiction. Pharmacopsychiatry 42(Suppl 1):S42–S55. doi:10.1055/s-0029-1216355

    Article  PubMed  Google Scholar 

  • Leng A, Feldon J, Ferger B (2004) Long-term social isolation and medial prefrontal cortex: dopaminergic and cholinergic neurotransmission. Pharmacol Biochem Behav 77:371–379. doi:10.1016/j.pbb.2003.11.011

    Article  CAS  PubMed  Google Scholar 

  • Logrip ML, Zorrilla EP, Koob GF (2012) Stress modulation of drug self-administration: implications for addiction comorbidity with post-traumatic stress disorder. Neuropharmacology 62(2):552–564. doi:10.1016/j.neuropharm.2011.07.007

    Article  CAS  PubMed  Google Scholar 

  • Maldonado C, Rodríguez-Arias M, Castillo A, Aguilar MA, Miñarro J (2006) Gamma-hydroxybutyric acid affects the acquisition and reinstatement of cocaine-induced conditioned place preference in mice. Behav Pharmacol 17(2):119–131. doi:10.1097/01.fbp.0000190685.84984.ec

    Article  CAS  PubMed  Google Scholar 

  • McCormick CM, Robarts D, Kopeikina K, Kelsey JE (2005) Long-lasting, sex- and age-specific effects of social stressors on corticosterone responses to restraint and on locomotor responses to psychostimulants in rats. Horm Behav 48:64–74. doi:10.1016/j.yhbeh.2005.01.008

    Article  CAS  PubMed  Google Scholar 

  • McLaughlin JP, Li S, Valdez J, Chavkin TA, Chavkin C (2006) Social defeat stress-induced behavioral responses are mediated by the endogenous kappa opioid system. Neuropsychopharmacology 31(6):1241–1248. doi:10.1038/sj.npp.1300872

    CAS  PubMed  PubMed Central  Google Scholar 

  • Miczek KA, Covington HE 3rd, Nikulina EM Jr, Hammer RP (2004) Aggression and defeat: persistent effects on cocaine self-administration and gene expression in peptidergic and aminergic mesocorticolimbic circuits. Neurosci Biobehav Rev 27(8):787–802. doi:10.1016/j.neubiorev.2003.11.005

    Article  CAS  PubMed  Google Scholar 

  • Miczek KA, Yap JJ, Covington HE 3rd (2008) Social stress, therapeutics and drug abuse: preclinical models of escalated and depressed intake. Pharmacol Ther 120(2):102–128. doi:10.1016/j.pharmthera.2008.07.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Montagud-Romero S, Aguilar MA, Maldonado C, Manzanedo C, Miñarro J, Rodríguez-Arias M (2015) Acute social defeat stress increases the conditioned rewarding effects of cocaine in adult but not in adolescent mice. Pharmacol Biochem Behav 135:1–12. doi:10.1016/j.pbb.2015.05.008

    Article  CAS  PubMed  Google Scholar 

  • Montagud-Romero S, Montesinos J, Pascual M, Aguilar MA, Roger-Sanchez C, Guerri C, Miñarro J, Rodríguez-Arias M (2016) Up-regulation of histone acetylation induced by social defeat mediates the conditioned rewarding effects of cocaine. Prog Neuro-Psychopharmacol Biol Psychiatry 70:39–48. doi:10.1016/j.pnpbp.2016.04.016

    Article  CAS  Google Scholar 

  • Montagud-Romero S, Daza-Losada M, Vidal-Infer A, Maldonado C, Aguilar MA, Miñarro J, Rodríguez-Arias M (2014) The novelty-seeking phenotype modulates the longlasting effects of intermittent ethanol administration during adolescence. PLoS One 9(3):e92576. doi:10.1371/journal.pone.0092576

    Article  PubMed  PubMed Central  Google Scholar 

  • Nikulina EM, Covington HE 3rd, Ganschow L, Hammer RP Jr, Miczek KA (2004) Long-term behavioral and neuronal cross-sensitization to amphetamine induced by repeated brief social defeat stress: Fos in the ventral tegmental area and amygdala. Neuroscience 123(4):857–865. doi:10.1016/j.neuroscience.2003.10.029

    Article  CAS  PubMed  Google Scholar 

  • Novick AM, Forster GL, Tejani-Butt SM, Watt MJ (2011) Adolescent social defeat alters markers of adult dopaminergic function. Brain Res Bull 86(1–2):123–128. doi:10.1016/j.brainresbull.2011.06.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pacchioni AM, Cador M, Bregonzio C, Cancela LM (2007) A glutamate-dopamine interaction in the persistent enhanced response to amphetamine in nucleus accumbens core but not shell following a single restraint stress. Neuropsychopharmacology 32(3):682–692. doi:10.1038/sj.npp.1301080

    Article  CAS  PubMed  Google Scholar 

  • Quadros IM, Miczek KA (2009) Two modes of intense cocaine bingeing: increased persistence after social defeat stress and increased rate of intake due to extended access conditions in rats. Psychopharmacology 206(1):109–120. doi:10.1007/s00213-009-1584-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Razzoli M, Andreoli M, Michielin F, Quarta D, Sokal DM (2011) Increased phasic activity of VTA dopamine neurons in mice 3 weeks after repeated social defeat. Behav Brain Res 218:253–257. doi:10.1016/j.bbr.2010.11.050

    Article  CAS  PubMed  Google Scholar 

  • Reddy N, Kasukurthi KB, Mahla RS, Pawar RM, Goel S (2012) Expression of vascular endothelial growth factor (VEGF) transcript and protein in the testis of several vertebrates, including endangered species. Theriogenology 77(3):608–614. doi:10.1016/j.theriogenology.2011.08.037

    Article  CAS  PubMed  Google Scholar 

  • Rodríguez-Arias M, García-Pardo MP, Montagud-Romero S, Miñarro J, Aguilar MA (2013) Role of stress in psychostimulant addiction: treatment approaches based on animal models. Drug use and abuse signs symptoms, physical and psychological effects and intervention approaches. Van Hout MC (Ed.) Hauppauge, NY: Nova Science.

  • Rodríguez-Arias M, Miñarro J, Aguilar MA, Pinazo J, Simón VM (1998) Effects of risperidone and SCH 23390 on isolation-induced aggression in male mice. Eur Neuropsychopharmacol 8(2):95–103. doi:10.1016/S0924-977X(97)00051-5

    Article  PubMed  Google Scholar 

  • Rodríguez-Arias M, Montagud-Romero S, Rubio-Araiz A, Aguilar MA, Martín-García E, Cabrera R, Maldonado R, Porcu F, Colado MI, Miñarro J (2015) Effects of repeated social defeat on adolescent mice on cocaine-induced CPP and self-administration in adulthood: integrity of the blood-brain barrier. Addict Biol. doi:10.1111/adb.12301 (in press)

    Google Scholar 

  • Rodríguez-Arias M, Navarrete F, Blanco-Gandia MC, Arenas MC, Bartoll-Andrés A, Aguilar MA, Rubio G, Miñarro J, Manzanares J (2016) Social defeat in adolescent mice increases vulnerability to alcohol consumption. Addict Biol 21(1):87–97. doi:10.1111/adb.12184

    Article  PubMed  Google Scholar 

  • Saal D, Dong Y, Bonci A, Malenka RC (2003) Drugs of abuse and stress trigger a common synaptic adaptation in dopamine neurons. Neuron 37:577–582. doi:10.1016/S0896-6273(03)00021-7

    Article  CAS  PubMed  Google Scholar 

  • Schäfer I, Teske L, Schulze-Thüsing J, Homann K, Reimer J, Haasen C, Hissbach J, Wiedemann K (2010) Impact of childhood trauma on hypothalamus-pituitary-adrenal axis activity in alcohol-dependent patients. Eur Addict Res 16(2):108–114. doi:10.1159/000294362

    Article  PubMed  Google Scholar 

  • Schneider M (2008) Puberty as a highly vulnerable developmental period for the consequences of cannabis exposure. Addict Biol 13(2):253–263. doi:10.1111/j.1369-1600.2008.00110.x

    Article  PubMed  Google Scholar 

  • Shirayama Y, Yang C, Zhang JC, Ren Q, Yao W, Hashimoto K (2015) Alterations in brain-derived neurotrophic factor (BDNF) in the brain regions of a learned helplessness rat model and the antidepressant effects of a TrkB agonist and antagonist. Eur Neuropsychopharmacol 25:2449–2458. doi:10.1016/j.euroneuro.2015.09.002

    Article  CAS  PubMed  Google Scholar 

  • Sinha R, Shaham Y, Heilig M (2011) Translational and reverse translational research on the role of stress in drug craving and relapse. Psychopharmacology 218(1):69–82. doi:10.1007/s00213-011-2263-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smits SM, Smidt MP (2006) The role of Pitx3 in survival of midbrain dopaminergic neurons. J Neural Transm Suppl 70:57–60. doi:10.1007/978-3-211-45295-0_10

    Article  CAS  Google Scholar 

  • Sun Y, Lim Y, Li F, Liu S, Lu JJ, Haberberger R, Zhong JH, Zhou XF (2012) ProBDNF collapses neurite outgrowth of primary neurons by activating RhoA. PLoS One 7(4):e35883. doi:10.1371/journal.pone.0035883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tidey JW, Miczek KA (1997) Acquisition of cocaine self-administration after social stress: role of accumbens dopamine. Psychopharmacology 130(3):203–212. doi:10.1007/s002130050230

    Article  CAS  PubMed  Google Scholar 

  • Tornatzky W, Miczek KA (1993) Long-term impairment of autonomic circadian rhythms after brief intermittent social stress. Physiol Behav 53(5):983–993. doi:10.1016/0031-9384(93)90278-N

    Article  CAS  PubMed  Google Scholar 

  • Vidal-Infer A, Arenas MC, Daza-Losada M, Aguilar MA, Miñarro J, Rodríguez-Arias M (2012) High novelty-seeking predicts greater sensitivity to the conditioned rewarding effects of cocaine. Pharmacol Biochem Behav 102(1):124–132. doi:10.1016/j.pbb.2012.03.031

    Article  CAS  PubMed  Google Scholar 

  • Watt MJ, Burke AR, Renner KJ, Forster GL (2009) Adolescent male rats exposed to social defeat exhibit altered anxiety behavior and limbic monoamines as adults. Behav Neurosci 123:564–576. doi:10.1037/a0015752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watt MJ, Roberts CL, Scholl JL, Meyer DL, Miiller LC, Barr JL, Novick AM, Renner KJ, Forster GL (2014) Decreased prefrontal cortex dopamine activity following adolescent social defeat in male rats: role of dopamine D2 receptors. Psychopharmacology 231:1627–1636. doi:10.1007/s00213-013-3353-9

    Article  CAS  PubMed  Google Scholar 

  • Woo NH, Teng HK, Siao CJ, Chiaruttini C, Pang PT, Milner TA, Hempstead BL, Lu B (2005) Activation of p75NTR by proBDNF facilitates hippocampal long-term depression. Nat Neurosci 8(8):1069–1077

    Article  CAS  PubMed  Google Scholar 

  • Xu ZQ, Sun Y, Li HY, Lim Y, Zhong JH, Zhou XF (2011) Endogenous proBDNF is a negative regulator of migration of cerebellar granule cells in neonatal mice. Eur J Neurosci 33(8):1376–1384. doi:10.1111/j.1460-9568.2011.07635.x

    Article  PubMed  Google Scholar 

  • Yang B, Yang CH, Ren Q, Zhang J-CH, Chen Q_X, Shirayama Y, Hashimoto K (2016) Regional differences in the expression of brain-derived neurotrophic factor (BDNF) pro-peptide, proBDNF and preproBDNF in the brain confer stress resilience. Eur Arch Psychiatry Clin Neurosci 266: 765–769. doi:10.1007/s00406-016-0693-6

  • Yap JJ, Miczek KA (2007) Social defeat stress, sensitization, and intravenous cocaine self-administration in mice. Psychopharmacology 192(2):261–273. doi:10.1007/s00213-007-0712-4

    Article  CAS  PubMed  Google Scholar 

  • Yeh FC, Kao CF, Kuo CF (2015) Explore the features of brain-derived neurotrophic factor in mood disorders. PLoS One 10:e0128605. doi:10.1371/journal.pone.0128605

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang JC, Yao W, Dong C, Yang C, Ren Q, Ma M, Han M, Hashimoto K (2015) Comparison of ketamine, 7,8-dihydroxyflavone, and ANA-12 antidepressant effect in the social defeat stress model of depression. Pschopharmacology (Berl) 232:4325–4335. doi:10.1007/s00213-015-4062-3

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Ministerio de Economia y Competitividad (MINECO), Direccion General de Investigacion, PSI2014-51847-R; Ministerio de Ciencia e Innovacion (SAF/FEDER 2013–49076-P), Spain; Instituto de Salud Carlos III, Red de Trastornos Adictivos (RTA) (RETICS RD06/0001/1006 and RD12/0028/0005), and Union Europea, Fondos FEDER: A way to build Europe; Fundacion Seneca (15405/PI/10), Region de Murcia, Spain; and Instituto Murciano de Investigacion en Biomedicina (IMIB), Region de Murcia, Spain, were acknowledged. We wish to thank Brian Normanly for his English language editing.

Author information

Authors and Affiliations

  1. Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez, 21, 46010, Valencia, Spain

    Sandra Montagud-Romero, M Carmen Blanco-Gandia, María A Aguilar, José Miñarro & Marta Rodríguez-Arias

  2. Murcia Research Institute of Health Sciences (IMIB) and Faculty of Medicine, University of Murcia, Murcia, Spain

    Cristina Nuñez, Elena Martínez-Laorden, Javier Navarro-Zaragoza, Pilar Almela, Maria-Victoria Milanés & María-Luisa Laorden

  3. Red Tematica de Investigacion Cooperativa en Salud (RETICS-Trastornos Adictivos), Instituto de Salud Carlos III, MICINN and FEDER, Madrid, Spain

    María A Aguilar, Maria-Victoria Milanés, María-Luisa Laorden, José Miñarro & Marta Rodríguez-Arias

Authors
  1. Sandra Montagud-Romero
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cristina Nuñez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Carmen Blanco-Gandia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elena Martínez-Laorden
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. María A Aguilar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Javier Navarro-Zaragoza
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Pilar Almela
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Maria-Victoria Milanés
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. María-Luisa Laorden
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. José Miñarro
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Marta Rodríguez-Arias
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marta Rodríguez-Arias.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Montagud-Romero, S., Nuñez, C., Blanco-Gandia, M.C. et al. Repeated social defeat and the rewarding effects of cocaine in adult and adolescent mice: dopamine transcription factors, proBDNF signaling pathways, and the TrkB receptor in the mesolimbic system. Psychopharmacology 234, 2063–2075 (2017). https://doi.org/10.1007/s00213-017-4612-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-017-4612-y

Keywords

Search

Navigation