Study of mirtazapine antidepressant effects in rats.

Mirtazapine is a widely used antidepressant and the aim of this study was to further investigate its antidepressant activity in rats. Thus, the efficacy of long-term mirtazapine treatment was assessed in three models of depressive symptoms induced by stress exposure: the acute escape deficit, the chronic escape deficit, and the stress-induced disruption of the acquisition of an appetitive behaviour sustained by a palatable food (vanilla sugar). Administration of mirtazapine for 2 wk prevented the escape deficit development induced by acute exposure to unavoidable stress. This protective effect was antagonized by the administration of a beta-adrenergic or a 5-HT1A receptor antagonist just before stress exposure; that is, mirtazapine effect was dependent on functional beta-adrenergic and 5-HT1A receptor systems. Repeated stress exposure indefinitely prolongs the condition of escape deficit and a 40-d mirtazapine treatment reversed this model of chronic escape deficit. In a Y-maze satiated rats learn to choose the arm baited with vanilla sugar, and exposure to stress during Y-maze training prevents this learning. Repeated mirtazapine administration completely antagonized the disrupting effect of chronic stress on the acquisition of this instrumental behaviour. We consider these effects to be crucial in the definition of antidepressant activity.