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Pharmacol Biochem Behav. 2009 Apr;92(2):267-71. doi: 10.1016/j.pbb.2008.12.008. Epub 2008 Dec 16.

Gamma1- and gamma2-melanocyte stimulating hormones induce central anxiogenic effects and potentiate ethanol withdrawal responses in the elevated plus-maze test in mice.

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  • 1Department of Pharmacology, Faculty of Medicine, University of Latvia, 1A Sarlotes St., LV-1001 Riga, Latvia.


Little is known about the endogenous functions of gamma1- and gamma2-melanocyte stimulating hormones (gamma1- and gamma2-MSH). Although gamma-MSHs bind to melanocortin receptor subtypes 3 and 4, we have previously shown that these peptides also influence non-melanocortinergic processes, such as dopaminergic and GABAergic. The aim of this study was to determine the effects of gamma1- and gamma2-MSH (at doses 0.3, 1 and 2 nmol/mouse/5 microl) on the anxiety levels in mice in elevated plus maze. Three experimental paradigms were performed to assess the effects of peptides on: a) ethanol withdrawal; b) acute ethanol-induced anxiolytic action; c) peptides per se. We used ethanol as the model substance, since its action involves either dopaminergic/GABAergic or melanocortinergic processes. gamma-MSHs were administered intracisternally in mice and behavioural responses were assessed in the elevated plus maze test. This study provides the first demonstration of an anxiogenic effect of gamma1- and gamma2-MSH, their synergistic/additive effect on ethanol withdrawal-induced anxiety behaviour, and an antagonism of peptides involved in the anxiolytic action of ethanol. Furthermore, results suggest that gamma-MSHs belong to an anxiogenic peptide family that may play an important role in anxiety disorders as well as in the development of alcohol dependence and/or alcohol withdrawal-induced behaviours.

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