title: Glucagon-like peptide 1 receptors in nucleus accumbens affect food intake.
abstract: Central glucagon-like peptide 1 receptor (GLP-1R) stimulation suppresses food intake, and hindbrain GLP-1 neurons project to numerous feeding-relevant brain regions. One such region is the nucleus accumbens (NAc), which plays a role in reward and motivated behavior. Using immunohistochemical and retrograde tracing techniques in rats, we identified a robust projection from GLP-1 neurons in the nucleus of the solitary tract to the NAc. We hypothesized that activation of NAc GLP-1Rs suppresses feeding. When injected into the NAc core of rats at doses subthreshold for effect when administered to the lateral ventricle, GLP-1 significantly reduced food intake relative to vehicle at 1, 2, and 24 h posttreatment. The same doses had no effect when injected into the NAc shell. NAc core treatment with ventricle-subthreshold doses of the GLP-1R antagonist exendin (9-39) caused significant hyperphagia at 2 h posttreatment, suggesting that endogenous stimulation of NAc core GLP-1Rs plays a role in limiting food intake. It has been suggested that GLP-1 can cause nausea, but we found that NAc core administration of GLP-1 did not cause a conditioned taste aversion to saccharin, suggesting that the anorexic effect of NAc core GLP-1 is not caused by malaise. Finally, we observed that NAc core injection of GLP-1 significantly increased c-Fos expression in the NAc core. We conclude that that GLP-1Rs in the NAc play a physiologic role in food intake control, and suggest that the GLP-1 projection to NAc core may link satiation signal processing in the hindbrain with forebrain processing of food reward.
authors: Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, Florida 32306-4301, USA.
authors: Amanda M
authors: AM
authors: Dossat
authors: Nicole
authors: N
authors: Lilly
authors: Kristen
authors: K
authors: Kay
authors: Diana L
authors: DL
authors: Williams
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism / Q000494:pharmacology; D000067757:Glucagon-Like Peptide-1 Receptor; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors / Q000502:physiology*; D012439:Saccharin / Q000008:administration & dosage; D013266:Stilbamidines; D013549:Sweetening Agents / Q000008:administration & dosage; D013649:Taste / Q000187:drug effects; D013997:Time Factors
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; D018027:Receptors, Glucagon; D013266:Stilbamidines; D013549:Sweetening Agents; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1; D012439:Saccharin