A neuropharmacologically-relevant animal model of depression

The phenomenon of "learned helplessness" was evaluated as a potential animal model of depression. Imipramine, but not chlorpromazine or lorazepam, had a delayed protective effect on the development of this behavior although lorazepam was effective after a single dose. Dose-response curves related either to concentration of imipramine in drinking water or to free drug levels in brain were linear with higher drug levels associated with a lowered degree of learned helplessness following chronic administration. The effects of imipramine on the development of learned helplessness were seen following four days of access to drug in drinking water, but not after 1, 2 or 3 days. This model, although clearly not a perfect fit with depression in humans, has many characteristics which suggest its utility in further studies of the mechanism of action of antidepressants.