Overlapping striatal sites mediate scopolamine-induced feeding suppression and mu-opioid-mediated hyperphagia in the rat
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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.
This study aimed to assess the overlap between the striatal sites mediating scopolamine-induced feeding suppression and mu-opioid-induced hyperphagia.
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.
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.
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.
KeywordsScopolamine Nucleus accumbens Striatum Opioid Feeding Anorexia Acetylcholine Motivation Rat Muscarinic receptor
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).
- 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 323–344Google Scholar
- 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 73:887–894PubMedCentralPubMedCrossRefGoogle Scholar
- 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) 17:1220–1225Google Scholar
- 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 54:3510–3516PubMedCrossRefGoogle Scholar