LISURIDE REDUCES PSYCHOMOTOR RETARDATION DURING WITHDRAWAL FROM CHRONIC INTRAVENOUS AMPHETAMINE SELF-ADMINISTRATION IN RATS

Withdrawal from chronic use of psychostimulant drugs in humans induces a clinical syndrome characterized by fatigue, psychomotor depression, anhedonia, and disturbances of sleep. Spontaneous locomotor activity and catalepsy were assessed in rats during withdrawal from a schedule of intravenous self-administration of high doses of amphetamine. At 2 and 4 days after cessation of amphetamine self-administration, rats showed a state Of psychomotor retardation as measured by reduction of locomotor activity and increased catalepsy. In search of a possible pharmacologic means of intervention for such behavioral changes, the effect of repeated treatment with the nonaddictive ergot derivative lisuride during the withdrawal phase was evaluated. At a dose devoid of any effects on locomotor activity, lisuride completely prevented the reduction in locomotor activity and the increase in catalepsy produced by amphetamine withdrawal. These results suggest the need for further studies on lisuride as a possible novel treatment during withdrawal from psychostimulant drugs in humans.