Role of melanin-concentrating hormone in the control of ethanol consumption: Region-specific effects revealed by expression and injection studies

The peptide melanin-concentrating hormone (MCH), produced mainly by cells in the lateral hypothalamus (LH), perifornical area (PF) and zona incerta (ZI), is suggested to have a role in the consumption of rewarding substances, such as ethanol, sucrose and palatable food. However, there is limited information on the specific brain sites where MCH acts to stimulate intake of these rewarding substances and on the feedback effects that their consumption has on the expression of endogenous MCH. The current study investigated MCH in relation to ethanol consumption, in Sprague–Dawley rats. In Experiment 1, chronic consumption of ethanol (from 0.70 to 2.7 g/kg/day) dose-dependently reduced MCH gene expression in the LH. In Experiments 2–4, the opposite effect was observed with acute oral ethanol, which stimulated MCH expression specifically in the LH but not the ZI. In Experiment 5, the effect of MCH injection in brain-cannulated rats on ethanol consumption was examined. Compared to saline, MCH injected in the paraventricular nucleus (PVN) and nucleus accumbens (NAc) selectively stimulated ethanol consumption without affecting food or water intake. In contrast, it reduced ethanol intake when administered into the LH, while having no effect in the ZI. These results demonstrate that voluntary, chronic consumption of ethanol leads to local negative feedback control of MCH expression in the LH. However, with a brief exposure, ethanol stimulates MCH-expressing neurons in this region, which through projections to the feeding-related PVN and reward-related NAc can promote further drinking behavior.

Research Highlights
► Chronic ethanol intake negatively feeds back to reduce hypothalamic MCH expression
► Acute ethanol stimulates MCH expression specifically in the lateral hypothalamus
► MCH selectively stimulates ethanol intake via projections to the PVN and NAc regions