Behavioral effects of cocaine and its interaction with d-amphetamine and morphine in rats

Abstract

Drugs of abuse are commonly co-abused, and frequently these combinations produce effects which cannot be predicted by studying the effects of the individual drugs. To investigate the behavioral interactions which occur following combinations of cocaine plus amphetamine or cocaine plus morphine, rats were trained to respond under a differential reinforcement of low rates (DRL) schedule (10–14 sec). Cocaine (0.1–10 mg/kg) and d-amphetamine (0.1–3 mg/kg) decreased the percentage of reinforced responses (efficiency) at doses which had no effect on overall rate of responding. Following moderate doses of either drug, the interresponse time (IRT) distribution showed an increase in the percentage of shorter (10 sec) IRT's. Morphine (0.1–10 mg/kg) also decreased efficiency, but the decrease which occured was only observed at doses which also decreased overall response rates. As might be expected, the IRT distribution for morphine showed a dose-related increase in the percentage of long IRT's (14 sec). When doses of morphine which had no significant effect when administered alone (1 or 3 mg/kg) were combined with cocaine, the cocaine dose-response curve for efficiency was shifted down and to the left and response rates were increased. Analysis of the IRT distribution showed that the combination of an ineffective dose of cocaine, 1 mg/kg, plus 3 mg/kg morphine produced a shift in the IRT distribution to the left (an increase in the percentage of short IRT's). When cocaine was combined with 0.3 mg/kg d-amphetamine, a dose which had no effect when given alone, no significant interactions were observed on efficiency or overall rate of responding. A higher dose of d-amphetamine (0.56 mg/kg) which significantly decreased efficiency and response rates when given alone, did not result in a greater effect when given in combination with cocaine.