Seasonal effects of the monoamine oxidase inhibitor deprenyl but not the tricyclic antidepressant imipramine in rats bred for helplessness

Abstract

Objective: Seasonal variations in monoaminergic function may underlie seasonal affective disorder, a subtype of major depression. Here, we examined whether antidepressant drugs which regulate monoaminergic function exhibit seasonal effects in an animal model of depression, congenital helplessness. Material and Method: Rats selectively bred for helplessness were required to press a lever to turn off a foot-shock before and after chronic treatment with the tricyclic antidepressant imipramine (10 mg/kg) or the monoamine oxidase inhibitor deprenyl (10 mg/kg). Control rats received saline. Different groups of rats were tested in summer-fall and spring over the course of two years. Results: Congenitally helpless (cH) rats that were treated with imipramine pressed the lever more often than controls in fall and in spring, indicative of antidepressant effects regardless of season. By contrast, cH rats treated with deprenyl pressed the lever more often in summer-fall than in spring, suggestive of seasonal drug effects on helplessness behavior. Deprenyl significantly attenuated the lever-pressing deficit in both seasons when compared to saline controls. Moreover, cH rats treated with deprenyl but not imipramine increased the number of lever presses over trials, indicative of negative reinforcement learning. Conclusion: The present data are the first to show seasonal variations in antidepressant drug effects that are possibly linked to changes in dopamine neurotransmission. The data support the view that we must take seasonality into account when evaluating the efficacy of antidepressant compounds.