Effects of repeated administration of cocaine on schedule-controlled behavior of rats.

The effects of cocaine (4.0--32 mg/kg) on schedule-controlled behavior of rats were determined before and during a period of repeated administration of cocaine. In rats trained to lever press on a fixed ratio 40 schedule for food delivery, cocaine (8.0--32 mg/kg) initially decreased response rate in a dose-related manner. During the period of repeated administration, the effects of cocaine on response rate and running rate were attenuated in 2 rats and did not change in 2 others. When dose-effect functions of cocaine were redetermined, a shift to the right was observed in several measures indicating the development of tolerance to these effects of cocaine on performance. In rats trained to lever press on a DRL 20" schedule for food delivery, cocaine (4.0--32 mg/kg) increased response rates, decreased number of reinforcements per session and shifted interresponse time distributions to the left (shorter IRT's in all rats). During the period of repeated administration, the effects of the daily dose of cocaine (16 mg/kg) on all these measures were attenuated. Tolerance to cocaine was further indicated by a shift in the dose effect function of cocaine to the right during the redetermination.