THE EFFECTS OF HALOPERIDOL AND CHLORPROMAZINE ON AMPHETAMINE METABOLISM AND AMPHETAMINE STEREOTYPE BEHAVIOR IN THE RAT

¹ Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland

Chlorpromazine has been used for the treatment of severe amphetamine toxicity. The present investigation compares the effects of chlorpromazine and haloperidol on amphetamine metabolism and the ability of each to block amphetamine stereotype behavior. In rats treated with chlorpromazine (15 mg/kg) or haloperidol (10 mg/kg) 30 minutes prior to the administration of H³-amphetamine, there was a slowing of the disappearance of H³-amphetamine from the brain. The half-life of the labeled amine increased to 140 minutes after chlorpromazine and to 69 minutes after haloperidol from a control value of 52 minutes in saline-pretreated control rats. After pretreatment with chlorpromazine (15 mg/kg) or haloperidol (10 mg/kg) only 29% and 80% (respectively) of the administered H³-amphetamine was metabolized in 3 hours by the whole rat as compared to 93% of the administered dose in control animals. Haloperidol (0.5 mg/kg) completely blocked amphetamine stereotype behavior whereas chlorpromazine in doses of 1 and 5 mg/kg only partially blocked this effect. Haloperidol in a dose which blocked amphetamine stereotype behavior had no inhibitory effect on amphetamine metabolism.