Participation of α-melanocyte stimulating hormone in ethanol-induced anxiolysis and withdrawal anxiety in rats

Although recent reports underscore a close association between the ethanol consumption and the central melanocortin (MC) system in rats, neurobehavioral component of this association has not been explored. In this study, we investigated the role of α-melanocyte stimulating hormone (α-MSH) in ethanol (1.5–2 g/kg, i.p.) induced anxiolysis and anxiety-like behavior following withdrawal from prolonged ethanol (9% v/v ethanol, 15 days) consumption, using elevated plus maze (EPM) test in rats. While α-MSH (1–5 μg/rat, i.c.v.) showed dose-dependent anxiogenic-like effect, the MC4 receptor antagonist HS014 (1–10 nM/rat, i.c.v.) or antiserum against α-MSH (1:500–1:50 dilution, 5 μl/rat, i.c.v.) failed to produce any effect in the EPM test. The anxiolytic-like effect of ethanol was suppressed by central administration of α-MSH (0.5 μg/rat, i.c.v.). On the other hand, pretreatment with either HS014 (5 nM/rat, i.c.v.) or antiserum against α-MSH (1:100 dilution, 5 μl/rat, i.c.v.) enhanced anxiolytic action of ethanol. Moreover, ethanol withdrawal anxiety was markedly blocked by HS014 (1–10 nM/rat, i.c.v.). These results suggest that α-MSH may be implicated in ethanol-induced anxiolysis and withdrawal anxiety. These findings also suggest MC4 receptors as possible therapeutic target for development of drugs to address the ethanol withdrawal-related conditions.