Exposure of rate to the behavioral despair test (an animal model of depression) for 40 min resulted in a long-lasting depletion of mesolimbic dopamine output to about 40% of baseline values. The decrease in extracellular dopamine was partially prevented by chronic pretreatment with imipramine (20 mg/kg per day i.p. for 21 days). The results suggest that a fall in mesolimbic dopamine output may be associated with depressive states and indicate that changes in the functional status of the dopamine system contribute to the mechanism of action of imipramine.