A further parametric study of imipramine in an animal model of depression.

We have proposed that chronic stress may produce motivational, behavioral, and neuroendocrine symptoms in rats resembling endogenous depression in humans. The chronic stress model has proved responsive to chronic treatment by antidepressant drugs. Two issues concerning this effect remain unresolved, these being; the requirement of drug chronicity, and treatment outcome to different drug doses. The present experiment examined both issues in a factorial design in which vehicle and two doses of the tricyclic antidepressant imipramine were varied across 2 treatment periods; acute (1 hr) and chronic (3 weeks). Both factors were found to significantly interact with treatment outcome, suggesting that chronic treatment is necessary for recovery and that this outcome is dependent upon drug level.