ALTERED EFFECTS OF DESIPRAMINE ON OPERANT PERFORMANCE AFTER 6-HYDROXYDOPAMINE-INDUCED DEPLETION OF BRAIN DOPAMINE OR NOREPINEPHRINE

Abstract

Performance maintained by differential-reinforcement-of-low-rate operant schedules is sensitive to antidepressant drugs. Tricyclic antidepressants, monoamine oxidase inhibitors and atypical antidepressants reduce response rate and increase reinforcement rate under long differential-reinforcement-of-low-rate schedules. In order to study the neurochemical mechanism by which the tricyclic antidepressant desipramine alters differential-reinforcement-of-low-rate performance, the effect of desipramine was determined before and after brain catecholamine depletion was induced by 6-hydroxydopamine administration in rats. Before lesioning, desipramine reduced response rate and increased reinforcement rate in a dose-dependent manner. Brain norepinephrine depletion (produced by 6-hydroxydopamine injection into the dorsal noradrenergic bundle) attenuated the ability of desipramine to reduce response rate, but did not alter its ability to increase reinforcement rate. Brain dopamine depletion, (produced by i.c.v. [intracerebroventricular] 6-hydroxydopamine administration after pargyline and desipramine pretreatment) attenuated the ability of desipramine to increase reinforcement rate. The sedative effect of desipramine may be mediated by its reinforcement with central norepinephrine neurons and the reinforcement rate-increasing effect may involve central dopamine neurons.