Feeding and behavioural effects of central administration of the melanocortin 3/4-R antagonist SHU9119 in obese and lean Siberian hamsters

Siberian hamsters accumulate fat reserves in long photoperiods, but show a long-term decrease in food intake and body weight when exposed to a short winter photoperiod. The aim of this study was to determine the role of central melanocortin 3/4 receptors (MC3/4-R) in generating this chronic catabolic state by investigating the effects of SHU9119, a MC3/4-R antagonist, on food intake and associated behaviours. In adult male hamsters, intra-cerebroventricular infusions of SHU9119 significantly increased food intake in a dose-dependent manner. The time course of action was slow, food intake being increased between 4 and 24 h after intra-cerebroventricular administration. A similar degree of increase in food intake occurred in fat hamsters in long days and in lean hamsters chronically exposed to short days. Intra-cerebroventricular treatment with MTII (a MC3/4-R agonist) significantly decreased food intake for up to 24 h after treatment, and SHU9119 reversed these suppressive effects between 4 and 24 h after treatment, a similar time course to that observed when SHU9119 was administered alone. We conclude that endogenous melanocortin peptides acting via MC3/4-R are involved in the regulation of food intake in hamsters in both anabolic and catabolic states, but these acute studies do not provide evidence that increased activity of this hypothalamic system underlies the seasonal decrease in food intake that contributes to the long-term catabolic state in short days. [Copyright &y& Elsevier]