Melanin-Concentrating Hormone Acutely Stimulates Feeding, But Chronic Administration Has No Effect on Body Weight

Melanin-concentrating hormone (MCH) has recently been proposed as both a central stimulator and an inhibitor of food intake. To clarify its role, we investigated the effects of MCH and the prepro-MCH-derived peptide neuropeptide E-I injected intracerebroventricularly (icv) in rats. MCH (0.15–15 μg) was injected icv at the beginning of the light phase. Food intake at 2 h showed a dose-dependent increase from 325 ± 7% of the control value (1.5-μg dose; P < 0.05) to 462 ± 30% of the control value (15-μg dose; P < 0.005). When 10 ng, 100 ng, and 5 μg MCH were injected icv at the beginning of the dark phase, only 5μ g stimulated feeding (166 ± 16% of the control value; P < 0.05). At no dose did MCH inhibit feeding. Twice daily icv injections of MCH (5 μg) caused an average 197± 9% increase in 2-h food intake for the first 5 days. Injections from days 6–8 did not stimulate feeding. Food intake and body weight at 24 h remained unchanged. Intracerbroventricular neuropeptide E-I had no effect on food intake alone and did not alter MCH-induced feeding. These studies show a dose-dependent stimulation of feeding by acute central administration of MCH. Tolerance is seen with chronic administration. These findings support a role for MCH in the immediate regulation of food intake, but not in body weight control.