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Eating Elicited by Orexin-A, But Not Melanin-Concentrating Hormone, Is Opioid Mediated

Department of Psychiatry, University of Cincinnati Medical Center (D.J.C., S.C.W., R.J.S.), Cincinnati, Ohio 45267-0559; and Departments of Biomedical Sciences and Cell Biology, Neurobiology, and Anatomy, University of Cincinnati Medical Center (E.L.A.), Cincinnati, Ohio 45267-0559

Address all correspondence and requests for reprints to: Deborah J. Clegg, Ph.D., Department of Psychiatry, University of Cincinnati Medical Center, P.O. Box 670559, Cincinnati, Ohio 45267-0559. E-mail: . debbie.clegg{at}uc.edu

Melanin-concentrating hormone (MCH) and orexin-A are orexigenic peptidergic neurotransmitters produced primarily in the lateral hypothalamus. Because two other hypothalamic peptides, neuropeptide Y and agouti-related peptide, increase food intake by a mechanism that depends on activation of opioid receptors, we assessed whether MCH or orexin-A also elicits food intake via opioid receptor activation. A dose of naloxone (0.3 mg/kg, ip) that had no effect on its own reduced the acute orexigenic effect of third ventricular (i3vt) orexin-A (3 ng/rat). However, this same dose of naloxone had no effect on i3vt MCH (5 µg/rat)-induced hyperphagia. Because the opioid system has also been linked to food selection, we investigated whether MCH or orexin-A alters food choice when rats have simultaneous access to two diets differing in the relative amounts of fat and carbohydrate. Whereas i3vt MCH stimulated intake of both diets and did not alter food choice, i3vt orexin-A stimulated intake of only the high fat diet. These data indicate that despite several similarities between MCH and orexin-A, these two lateral hypothalamic area peptides stimulate food intake by recruiting different neural circuits and exert different effects on food choice.

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