Abstract
Melanin‐concentrating hormone (MCH) is a cyclic, 19‐amino‐acid neuropeptide produced in the lateral hypothalamus. MCH is implicated in a number of physiological processes including feeding behavior, energy balance, reproductive function, memory, sleep‐wake regulation, and emotional states. Since the discoveries in the mid‐1990 s that MCH is an appetite stimulant in rodents and that KO mice lacking MCH become lean, together with the findings that MCH receptor 1 (MCH1R) is responsible for these functions, most research has been focused on the roles of the MCH system in feeding and energy homeostasis. It is now established that MCH plays a key role in controlling feeding and energy homeostasis via MCH1R, and some pharmaceutical companies have reported nonpeptidic MCH1R antagonists with diverse structural features in the treatment of obesity. Recently, emerging lines of evidence have indicated that MCH1R plays important roles not only in feeding and energy balance but also in regulation of emotion. Indeed, MCH1R is widely distributed in the regions associated with emotion, and MCH1R antagonists have been demonstrated to exhibit antidepressant and anxiolytic effects in various rodent models. This review describes recent advances in research to clarify the involvement of MCH in depression and anxiety. The paper will also discuss the potential value of MCH1R antagonists in the treatment of depressive and anxiety disorders. Drug Dev. Res. 65:278–290, 2005. © 2005 Wiley‐Liss, Inc.