Abstract
Rationale
Intra-striatal infusions of the muscarinic antagonist, scopolamine, markedly suppress feeding; however, the underlying mechanisms are unclear. Recent findings suggest that scopolamine influences opioid-dependent mechanisms of feeding modulation. Robust mu-opioid-mediated feeding responses are obtained in anterior, ventral sectors of the striatum with progressively weaker effects posteriorly and dorsally. One might therefore expect the effects of scopolamine to conform to similar boundaries, but a systematic mapping of scopolamine-induced feeding suppression has not yet been undertaken.
Objective
This study aimed to assess the overlap between the striatal sites mediating scopolamine-induced feeding suppression and mu-opioid-induced hyperphagia.
Methods
Dose–effect functions for scopolamine (0, 1, 5, and 10 μg) were obtained in the nucleus accumbens (Acb), anterior dorsal striatum (ADS), and posterior dorsal striatum (PDS) in three different groups of rats. In the same subjects, the mu-opioid receptor agonist (d-Ala2-N-MePhe4, Glyol)-enkephalin (DAMGO; 0.25 μg) was infused on a separate test day. The dependent variables were food and water intake, ambulation, and rearing.
Results
The greatest dose sensitivity for scopolamine-induced feeding suppression was observed in the Acb. Only the highest dose was effective in the ADS, and no effects were seen in the PDS. Water intake and general motor activity were not altered by scopolamine in any site. DAMGO infusions produced hyperphagia only in the Acb.
Conclusions
These results support a model in which the behavioral effects of muscarinic blockade are limited by the same anatomical constraints that govern mu-opioid receptor-mediated control of feeding. These constraints are likely imposed by the topographic arrangement of feeding-related afferent inputs and efferent projections of the striatum.
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References
Aosaki T, Kimura M, Graybiel AM (1995) Temporal and spatial characteristics of tonically active neurons of the primate’s striatum. J Neurophysiol 73:1234–1252
Avena NM, Rada P, Moise N, Hoebel BG (2006) Sucrose sham feeding on a binge schedule releases accumbens dopamine repeatedly and eliminates the acetylcholine satiety response. Neuroscience 139:813–820
Azzara AV, Bodnar RJ, Delamater AR, Sclafani A (2000) Naltrexone fails to block the acquisition or expression of a flavor preference conditioned by intragastric carbohydrate infusions. Pharmacol Biochem Behav 67:545–557
Bakshi VP, Kelley AE (1993a) Feeding induced by opioid stimulation of the ventral striatum: role of opiate receptor subtypes. J Pharmacol Exp Ther 265:1253–1260
Bakshi VP, Kelley AE (1993b) Striatal regulation of morphine-induced hyperphagia: an anatomical mapping study. Psychopharmacology (Berl) 111:207–214
Baldo BA, Daniel RA, Berridge CW, Kelley AE (2003) Overlapping distributions of orexin/hypocretin- and dopamine-beta-hydroxylase immunoreactive fibers in rat brain regions mediating arousal, motivation, and stress. J Comp Neurol 464:220–237
Baldo BA, Kelley AE (2007) Discrete neurochemical coding of distinguishable motivational processes: insights from nucleus accumbens control of feeding. Psychopharmacology (Berl) 191:439–459
Baldo BA, Pratt WE, Kelley AE (2010) Control of fat intake by striatal opioids. In: Montmayeur JP, Le Coutre J (eds) Fat detection: taste, texture, and postingestive effects (frontiers in neuroscience). CRC, Boca Raton, pp 323–344
Barbano MF, Le Saux M, Cador M (2009) Involvement of dopamine and opioids in the motivation to eat: influence of palatability, homeostatic state, and behavioral paradigms. Psychopharmacology (Berl) 203:475–487
Berendse HW, Galis-de Graaf Y, Groenewegen HJ (1992) Topographical organization and relationship with ventral striatal compartments of prefrontal corticostriatal projections in the rat. J Comp Neurol 316:314–347
Berridge KC (2007) The debate over dopamine’s role in reward: the case for incentive salience. Psychopharmacology (Berl) 191:391–431
Bittencourt JC, Presse F, Arias C, Peto C, Vaughan J, Nahon JL, Vale W, Sawchenko PE (1992) The melanin-concentrating hormone system of the rat brain: an immuno- and hybridization histochemical characterization. J Comp Neurol 319:218–245
Boix-Trelis N, Vale-Martinez A, Guillazo-Blanch G, Marti-Nicolovius M (2007) Muscarinic cholinergic receptor blockade in the rat prelimbic cortex impairs the social transmission of food preference. Neurbiol Learn Mem 87:659–668
Cambridge VC, Ziauddeen H, Nathan PJ, Subramaniam N, Dodds C, Chamberlain SR, Koch A, Maltby K, Skeggs AL, Napolitano A, Farooqi IS, Bullmore ET, Fletcher PC (2013) Neural and behavioral effects of a novel mu opioid receptor antagonist in binge-eating obese people. Biol Psychiatry 73:887–894
Cunningham ST, Kelley AE (1992) Opiate infusion into nucleus accumbens: contrasting effects on motor activity and responding for conditioned reward. Brain Res 588:104–114
Davis CA, Levitan RD, Reid C, Carter JC, Kaplan AS, Patte KA, King N, Curtis C, Kennedy JL (2009) Dopamine for "wanting" and opioids for "liking": a comparison of obese adults with and without binge eating. Obesity (Silver Spring) 17:1220–1225
DiFeliceantonio AG, Mabrouk OS, Kennedy RT, Berridge KC (2012) Enkephalin surges in dorsal striatum as a signal to eat. Curr Biol 22:1918–1924
Gosnell BA, Levine AS (2009) Reward systems and food intake: role of opioids. Int J Obes (Lond) 33(Suppl 2):S54–S58
Groenewegen HJ, Wright CI, Beijer AV, Voorn P (1999) Convergence and segregation of ventral striatal inputs and outputs. Ann N Y Acad Sci 877:49–63
Haber SN, Calzavara R (2009) The cortico-basal ganglia integrative network: the role of the thalamus. Brain Res Bull 78:69–74
Haber SN, Kim KS, Mailly P, Calzavara R (2006) Reward-related cortical inputs define a large striatal region in primates that interface with associative cortical connections, providing a substrate for incentive-based learning. J Neurosci 26:8368–8376
Hata T, Okaichi H (2004) Medial prefrontal cortex and precision of temporal discrimination: a lesion, microinjection, and microdialysis study. Neurosci Res 49:81–89
Heimer L, Zahm DS, Churchill L, Kalivas PW, Wohltmann C (1991) Specificity in the projection patterns of accumbal core and shell in the rat. Neuroscience 41:89–125
Hersch SM, Gutekunst CA, Rees HD, Heilman CJ, Levey AI (1994) Distribution of m1–m4 muscarinic receptor proteins in the rat striatum: light and electron microscopic immunocytochemistry using subtype-specific antibodies. J Neurosci 14:3351–3363
Hoebel BG, Avena NM, Rada P (2007) Accumbens dopamine–acetylcholine balance in approach and avoidance. Curr Opin Pharmacol 7:617–627
Hoebel BG, Hernandez L, Schwartz DH, Mark GP, Hunter GA (1989) Microdialysis studies of brain norepinephrine, serotonin, and dopamine release during ingestive behavior. Theoretical and clinical implications. Ann N Y Acad Sci 575:171–191, discussion 192–3
Izzo PN, Bolam JP (1988) Cholinergic synaptic input to different parts of spiny striatonigral neurons in the rat. J Comp Neurol 269:219–234
Joyce EM, Koob GF (1981) Amphetamine-, scopolamine- and caffeine-induced locomotor activity following 6-hydroxydopamine lesions of the mesolimbic dopamine system. Psychopharmacology (Berl) 73:311–313
Kas MJ, van den Bos R, Baars AM, Lubbers M, Lesscher HM, Hillebrand JJ, Schuller AG, Pintar JE, Spruijt BM (2004) Mu-opioid receptor knockout mice show diminished food-anticipatory activity. Eur J Neurosci 20:1624–1632
Kelley AE, Baldo BA, Pratt WE (2005a) A proposed hypothalamic–thalamic–striatal axis for the integration of energy balance, arousal, and food reward. J Comp Neurol 493:72–85
Kelley AE, Baldo BA, Pratt WE, Will MJ (2005b) Corticostriatal-hypothalamic circuitry and food motivation: integration of energy, action and reward. Physiol Behav 86:773–795
Kelley AE, Swanson CJ (1997) Feeding induced by blockade of AMPA and kainate receptors within the ventral striatum: a microinfusion mapping study. Behav Brain Res 89:107–113
Mark GP, Rada P, Pothos E, Hoebel BG (1992) Effects of feeding and drinking on acetylcholine release in the nucleus accumbens, striatum, and hippocampus of freely behaving rats. J Neurochem 58:2269–2274
McGeorge AJ, Faull RL (1987) The organization and collateralization of corticostriate neurones in the motor and sensory cortex of the rat brain. Brain Res 423:318–324
McGeorge AJ, Faull RL (1989) The organization of the projection from the cerebral cortex to the striatum in the rat. Neuroscience 29:503–537
Miura M, Masuda M, Aosaki T (2008) Roles of micro-opioid receptors in GABAergic synaptic transmission in the striosome and matrix compartments of the striatum. Mol Neurobiol 37:104–115
Mogenson GJ, Jones DL, Yim CY (1980) From motivation to action: functional interface between the limbic system and the motor system. Prog Neurobiol 14:69–97
Palmiter RD (2008) Dopamine signaling in the dorsal striatum is essential for motivated behaviors: lessons from dopamine-deficient mice. Ann N Y Acad Sci 1129:35–46
Papaleo F, Kieffer BL, Tabarin A, Contarino A (2007) Decreased motivation to eat in mu-opioid receptor-deficient mice. Eur J Neurosci 25:3398–3405
Patterson CM, Leshan RL, Jones JC, Myers MG Jr (2011) Molecular mapping of mouse brain regions innervated by leptin receptor-expressing cells. Brain Res 1378:18–28
Pecina S, Berridge KC (2005) Hedonic hot spot in nucleus accumbens shell: where do mu-opioids cause increased hedonic impact of sweetness? J Neurosci 25:11777–11786
Perry ML, Andrzejewski ME, Bushek SM, Baldo BA (2010) Intra-accumbens infusion of a muscarinic antagonist reduces food intake without altering the incentive properties of food-associated cues. Behav Neurosci 124:44–54
Perry ML, Baldo BA, Andrzejewski ME, Kelley AE (2009) Muscarinic receptor antagonism causes a functional alteration in nucleus accumbens mu-opiate-mediated feeding behavior. Behav Brain Res 197:225–229
Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG, Kilduff TS (1998) Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 18:9996–10015
Phelps PE, Houser CR, Vaughn JE (1985) Immunocytochemical localization of choline acetyltransferase within the rat neostriatum: a correlated light and electron microscopic study of cholinergic neurons and synapses. J Comp Neurol 238:286–307
Pratt WE, Blackstone K (2009) Nucleus accumbens acetylcholine and food intake: decreased muscarinic tone reduces feeding but not food-seeking. Behav Brain Res 198:252–257
Pratt WE, Kelley AE (2004) Nucleus accumbens acetylcholine regulates appetitive learning and motivation for food via activation of muscarinic receptors. Behav Neurosci 118:730–739
Pratt WE, Kelley AE (2005) Striatal muscarinic receptor antagonism reduces 24-h food intake in association with decreased preproenkephalin gene expression. Eur J Neurosci 22:3229–3240
Ragozzino ME, Kesner RP (1998) The effects of muscarinic cholinergic receptor blockade in the rat anterior cingulate and prelimbic/infralimbic cortices on spatial working memory. Neurobiol Learn Mem 69:241–257
Reynolds SM, Zahm DS (2005) Specificity in the projections of prefrontal and insular cortex to ventral striatopallidum and the extended amygdala. J Neurosci 25:11757–11767
Salamone JD, Correa M, Farrar A, Mingote SM (2007) Effort-related functions of nucleus accumbens dopamine and associated forebrain circuits. Psychopharmacology (Berl) 191:461–482
Stratford TR, Kelley AE (1997) GABA in the nucleus accumbens shell participates in the central regulation of feeding behavior. J Neurosci 17:4434–4440
Sullivan MA, Chen H, Morikawa H (2008) Recurrent inhibitory network among striatal cholinergic interneurons. J Neurosci 28:8682–8690
Tabarin A, Diz-Chaves Y, Carmona Mdel C, Catargi B, Zorrilla EP, Roberts AJ, Coscina DV, Rousset S, Redonnet A, Parker GC, Inoue K, Ricquier D, Penicaud L, Kieffer BL, Koob GF (2005) Resistance to diet-induced obesity in mu-opioid receptor-deficient mice: evidence for a "thrifty gene". Diabetes 54:3510–3516
Thompson RH, Swanson LW (2010) Hypothesis-driven structural connectivity analysis supports network over hierarchical model of brain architecture. Proc Natl Acad Sci U S A 107:15235–15239
Voorn P, Vanderschuren LJ, Groenewegen HJ, Robbins TW, Pennartz CM (2004) Putting a spin on the dorsal-ventral divide of the striatum. Trends Neurosci 27:468–474
Wang JQ, McGinty JF (1996) Muscarinic receptors regulate striatal neuropeptide gene expression in normal and amphetamine-treated rats. Neuroscience 75:43–56
Will MJ, Pratt WE, Kelley AE (2006) Pharmacological characterization of high-fat feeding induced by opioid stimulation of the ventral striatum. Physiol Behav 89:226–234
Woolley JD, Lee BS, Fields HL (2006) Nucleus accumbens opioids regulate flavor-based preferences in food consumption. Neuroscience 143:309–317
Woolley JD, Lee BS, Taha SA, Fields HL (2007) Nucleus accumbens opioid signaling conditions short-term flavor preferences. Neuroscience 146:19–30
Zahm DS, Heimer L (1993) Specificity in the efferent projections of the nucleus accumbens in the rat: comparison of the rostral pole projection patterns with those of the core and shell. J Comp Neurol 327:220–232
Zhang M, Balmadrid C, Kelley AE (2003) Nucleus accumbens opioid, GABaergic, and dopaminergic modulation of palatable food motivation: contrasting effects revealed by a progressive ratio study in the rat. Behav Neurosci 117:202–211
Zhang M, Kelley AE (2000) Enhanced intake of high-fat food following striatal mu-opioid stimulation: microinjection mapping and fos expression. Neuroscience 99:267–277
Zhang M, Kelley AE (2002) Intake of saccharin, salt, and ethanol solutions is increased by infusion of a mu opioid agonist into the nucleus accumbens. Psychopharmacology (Berl) 159:415–423
Zhou FM, Wilson CJ, Dani JA (2002) Cholinergic interneuron characteristics and nicotinic properties in the striatum. J Neurobiol 53:590–605
Acknowledgments
We would like to thank Drs. Matthew Andrzejewski, Brenda McKee, and Robert Twining for helpful comments on the manuscript. This research was supported by grants from National Institute on Drug Abuse (RO1 DA 009311 and F31 DA 023775) and National Institute of Mental Health (RO1 MH 074723).
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Perry, M.L., Pratt, W.E. & Baldo, B.A. Overlapping striatal sites mediate scopolamine-induced feeding suppression and mu-opioid-mediated hyperphagia in the rat. Psychopharmacology 231, 919–928 (2014). https://doi.org/10.1007/s00213-013-3317-0
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DOI: https://doi.org/10.1007/s00213-013-3317-0