Gamma1- and gamma2-melanocyte stimulating hormones induce central anxiogenic effects and potentiate ethanol withdrawal responses in the elevated plus-maze test in mice.
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.
Jansone
Baiba
B
Department of Pharmacology, Faculty of Medicine, University of Latvia, 1A Sarlotes St., LV-1001 Riga, Latvia. baijansone@inbox.lv
Rumaks
Juris
J
Dzirkale
Zane
Z
Pupure
Jolanta
J
Svirskis
Simons
S
Muceniece
Ruta
R
Klusa
Vija
V
D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects*; D008297:Male; D018782:Maze Learning; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D013375:Substance Withdrawal Syndrome / Q000209:etiology*
D000431:Ethanol; D009074:Melanocyte-Stimulating Hormones