PROGESTERONE MODULATION OF ANXIETY AND DOPAMINERGIC MESOLIMBIC SYSTEM OF THE BRAIN ACTIVITY IN RATS WITH ALCOHOL DEPENDENCE AND UNDER CONDITIONS OF ZOOSOCIAL CONFLICT

Abstract

Exogenous modulation by progesterone of the central neurosteroid mechanisms of regulation of anxiety and its important component, the activity of the mesolimbic dopaminergic system, is a promising method of correction of emotional behavioral disorders. The aim of this work was to study the effect of intranasal progesterone administration on the baseline level of anxiety and the activity of the dopaminergic mesolimbic brain system in alcohol-dependent and zoosocial conflict rats. Neuroethological studies by the method of assessing the individual level of anxiety. The levels of catecholamines (dopamine, noradrenaline, adrenaline) in the brain structures were determined by the method of immunoenzymatic analysis. Emotional stress, namely zoosocial instability and confrontational interactions, was modeled using the sensory contact technique and the partition test. Alcohol dependence in rats was induced by voluntary consumption of alcohol-containing food. Progesterone was administered intranasally at a dose of 80 μg per animal. It is shown that the level of anxiety in rats under conditions of alcohol dependence and emotional stress is associated with dopamine and adrenergic disturbances in the ventral tegmental area (VTA) and nucleus accumbens. The anxiolytic effects of progesterone are manifested in the suppression of the increase in anxiety following exposure to emotional stress in alcohol-dependent rats and its suppression in rats with baseline low levels of anxiety following repeated exposure to emotional stress. A balanced activation of the dopaminergic mesolimbic system during progesterone administration leads to the formation of a new allostatic state in rats with a decrease in anxiety levels.