Comparative behavioral profile of cocaine and norcocaine in rats and monkeys

The effects of cocaine and norcocaine were compared using locomotor activity, fixed-ratio 100 (FR 100) and fixed-interval 4 min (FI 4 min) food reinforcement and free feeding paradigms in rat and intravenous self-administration tests in rhesus monkeys. Cocaine was shown to significantly increase locomotor activity at doses of 20 and 40 mg/kg, while norcocaine had no effect at these doses and produced convulsions and death at 60 and 80 mg/kg. Both compounds significantly reduced food consumption at one or more of the doses tested. Cocaine and norcocaine at doses of 20 and 40 mg/kg, produced decreases in FR responding. Cocaine at doses of 10, 20, and 40 mg/kg, produced increases in FI responding; norcocaine had no effect following 10 mg/kg and decreased responding at 20 and 40 mg/kg. Cocaine (0.2 mg/kg/inj) and norcocaine (0.5, 0.2, 0.8 mg/kg/inj) maintained intravenous self-administration in all three monkeys tested. The data indicate that norcocaine is a pharmacologically active metabolite of cocaine which could account for some of the activity heretofore attributed to cocaine. However, the lack of any stimulatory effect of norcocaine or locomotor activity and the lack of increased responding produced by norcocaine on fixed-interval behavior suggest that norcocaine differs qualitatively from cocaine.