γ1- and γ2-melanocyte stimulating hormones induce central anxiogenic effects and potentiate ethanol withdrawal responses in the elevated plus-maze test in mice

Date
2009
Authors
Jansone, Baiba
Rumaks, Juris
Dzirkale, Zane
Pupure, Jolanta
Svirskis, Šimons
Muceniece, Ruta
Klusa, Vija
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Abstract
Little is known about the endogenous functions of γ1- and γ2-melanocyte stimulating hormones (γ1- and γ2-MSH). Although γ-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 γ1- and γ2-MSH (at doses 0.3, 1 and 2 nmol/mouse/5 μl) 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. γ-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 γ1- and γ2-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 γ-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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Keywords
Research Subject Categories::MEDICINE , γ1-MSH , γ2-MSH , Anxiety , Ethanol withdrawal responses , Elevated plus-maze test
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