Antidepressant, anxiolytic and anorectic effects of a melanin-concentrating hormone-1 receptor antagonist

• Published in: Nature medicine Vol. 8; no. 8; pp. 825 - 830
• Main Authors: Forray, Carlos, Borowsky, Beth, Durkin, Margaret M, Ogozalek, Kristine, Marzabadi, Mohammad R, DeLeon, John, Heurich, Rainer, Lichtblau, Harvey, Shaposhnik, Zoya, Daniewska, Irena, Blackburn, Thomas P, Branchek, Theresa A, Gerald, Christophe, Vaysse, Pierre J
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.08.2002
• Subjects: Analysis; Animal behavior; Animal models; Animals; Anti-Anxiety Agents - pharmacology; Antidepressants; Antidepressive Agents - pharmacology; Anxiety; Appetite Depressants - pharmacology; Behavior, Animal - drug effects; Binding sites; Body weight; Body Weight - drug effects; Brain - cytology; Brain - metabolism; Cell Line; Diet; Eating - drug effects; Energy balance; Female; Food; Guinea Pigs; Humans; Hypothalamic Hormones - chemistry; Hypothalamic Hormones - metabolism; Hypothalamus; Ligands; Male; Melanins - chemistry; Melanins - metabolism; Mental depression; Molecular Structure; Neuropeptides; Obesity; Physiological aspects; Piperidines - pharmacology; Pituitary Hormones - chemistry; Pituitary Hormones - metabolism; Pyrimidines - pharmacology; Random Allocation; Rats; Rats, Long-Evans; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Pituitary Hormone - antagonists & inhibitors; Receptors, Pituitary Hormone - metabolism; Social behavior; Tranquilizers
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm741

Melanin concentrating hormone (MCH) is an orexigenic hypothalamic neuropeptide, which plays an important role in the complex regulation of energy balance and body weight. Here we show that SNAP-7941, a selective, high-affinity MCH1 receptor (MCH1-R) antagonist, inhibited food intake stimulated by central administration of MCH, reduced consumption of palatable food, and, after chronic administration to rats with diet-induced obesity, resulted in a marked, sustained decrease in body weight. In addition, after mapping the binding sites for [(3)H]SNAP-7941 in rat brain, we evaluated its effects in a series of behavioral models. SNAP-7941 produced effects similar to clinically used antidepressants and anxiolytics in three animal models of depression/anxiety: the rat forced-swim test, rat social interaction and guinea pig maternal-separation vocalization tests. Given these observations, an MCH1-R antagonist may be useful not only in the management of obesity but also as a treatment for depression and/or anxiety.