Drug effects on response-duration differentiation. II: Selective effects of antidepressant drugs

Preclinical assays used to screen for antidepressant activity have traditionally been limited in their ability to selectively detect antidepressants. In the present study, we assessed the effects of antidepressant and non-antidepressant drugs on response-duration differentiation responding as a potential screen for antidepressant activity. Under this schedule, rats were trained to hold a lever in the down position for a duration greater than 1 sec but not more than 1.3 sec. The effects of the monoamine oxidase inhibitor tranylcypromine, the tricyclics imipramine and amitriptyline, and the atypical antidepressants trazadone and bupropion, as well as haloperidol, chlorpromazine, scopolamine and diazepam were studied. The antidepressant drugs selectively produced increases in the mean response durations. The non-antidepressant drugs produced much shorter mean response durations, although diazepam and chlorpromazine also increased the proportion of response durations that were greater than 1.3 sec. The order of potency of the antidepressants for increasing mean response durations corresponded well with their clinical potencies, suggesting that response-duration differentiation may be useful in screening for antidepressant activity.