Chronic Loss of Melanin-Concentrating Hormone Affects Motivational Aspects of Feeding in the Rat

J.D. Mul, S.E. la Fleur, P.W. Toonen, R. Binnekade, D. Schetters, M.M.M. Verheij, R.M. Sears, J. Homberg, A.N.M. Schoffelmeer, R.A.H. Adan, R.J. DiLeone, T.J. de Vries, E. Cuppen

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Abstract

Current epidemic obesity levels apply great medical and financial pressure to the strenuous economy of obesity-prone cultures, and neuropeptides involved in body weight regulation are regarded as attractive targets for a possible treatment of obesity in humans. The lateral hypothalamus and the nucleus accumbens shell (AcbSh) form a hypothalamic-limbic neuropeptide feeding circuit mediated by Melanin-Concentrating Hormone (MCH). MCH promotes feeding behavior via MCH receptor-1 (MCH1R) in the AcbSh, although this relationship has not been fully characterized. Given the AcbSh mediates reinforcing properties of food, we hypothesized that MCH modulates motivational aspects of feeding. Here we show that chronic loss of the rat MCH-precursor Pmch decreased food intake predominantly via a reduction in meal size during rat development and reduced high-fat food-reinforced operant responding in adult rats. Moreover, acute AcbSh administration of Neuropeptide-GE and Neuropeptide-EI (NEI), both additional neuropeptides derived from Pmch, or chronic intracerebroventricular infusion of NEI, did not affect feeding behavior in adult pmch
Original languageEnglish
Article numbere19600
JournalPLoS ONE
Volume6
Issue number5
DOIs
Publication statusPublished - 2011

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