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

Division of Endocrinology and Metabolic Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom W12 0NN

Address all correspondence and requests for reprints to: Prof. S. R. Bloom, Division of Endocrinology and Metabolic Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London, United Kingdom W12 0NN. E-mail: sbloom{at}rpms.ac.uk

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 5 µg 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.

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