Alcohol's modulation of cocaine-induced place preferences: Serial and concurrent interactions

In humans, alcohol consumption commonly precedes and co-occurs with cocaine use, suggesting that alcohol may act as a significant catalyst for the initiation and maintenance of cocaine use. Although the bases for these interactions are unknown, it is possible that alcohol influences the likelihood to begin, maintain and reinitiate cocaine use by modulating cocaine reinforcement. Therefore, the purpose of the present assessments was to examine alcohol's ability to modulate cocaine reinforcement using a drug abuse model (i.e., the conditioned place preference design) sensitive to drug interactions similar to those that occur in the human cocaine using population. Specifically, Experiment 1 assessed the effects of alcohol preexposure (1.5 g/kg) on place preferences conditioned by 20 mg/kg cocaine. Experiment 2a and 2b examined the effects of alcohol (0.5g/kg) on place preferences conditioned by low (2.5 and 5 mg/kg; Experiment 2a), intermediate (20 mg/kg; Experiment 2b) and high (30 and 40 mg/kg; Experiment 2b) doses of cocaine when these two compounds are administered concurrently. Finally, Experiment 3 assessed the ability of alcohol (0.5 and 1.0 g/kg) to reinstate place preferences conditioned by 20 mg/kg cocaine. In Experiment 1, cocaine's ability to condition a place preference was not altered after animals were preexposed to alcohol, suggesting that alcohol history produced no measurable change in cocaine's reinforcing effects. In Experiment 2a and 2b, however, alcohol potentiated the place conditioning effects of 5 mg/kg cocaine, had no effect on place preferences produced by 20 mg/kg cocaine and attenuated place preferences conditioned by 30 and 40 mg/kg cocaine. These data indicate that alcohol produced a bi-directional modulation in cocaine reinforcement that was selective to cocaine dose. Finally, in Experiment 3, priming injections of 0.5 and 1.0 g/kg alcohol failed to reinstate cocaine place preferences previously conditioned by 20 mg/kg cocaine, suggesting that alcohol did not renew the salience of cocaine reinforcement in animals with previous cocaine experience. Together, these findings suggest that within the CPP design, only the concurrent administration of cocaine and alcohol produced measurable changes in cocaine's reinforcing effects.