The interaction of cocaethylene and cocaine and of cocaethylene and alcohol on schedule-controlled responding in rats

Abstract 

Rationale: Cocaethylene is a unique metabolite of cocaine, produced only in the presence of alcohol. This metabolite is pharmacologically, physiologically and behaviorally active. Further, it has been reported to interact pharmacokinetically with both cocaine and alcohol, an interaction that may mediate, in part, the interaction of cocaine and alcohol. Although cocaethylene has been shown to interact with both cocaine and alcohol, behavioral assessments of these interactions are limited. Objectives: To examine directly the behavioral interactions between cocaethylene and cocaine and between cocaethylene and alcohol, the present study assessed the effects produced by these combinations on schedule-controlled responding. Methods: Rats were first administered cumulative doses of cocaethylene, cocaine and alcohol to assess their effects alone on responding. Following this, doses of cocaethylene were combined with cumulative doses of cocaine or alcohol. Additionally, doses of cocaine or alcohol were given in combination with cumulative doses of cocaethylene. Results: When administered alone, cocaethylene, cocaine and alcohol produced dose-related decreases in responding. Further, cocaethylene shifted the dose–response functions for both cocaine and alcohol to the left and down, while cocaine and alcohol shifted the dose–response function for cocaethylene to the left and down. An isobolographic analysis revealed that these interactions were additive in nature. Conclusions: The present study suggests behavioral interactions between cocaethylene and cocaine and between cocaethylene and alcohol. The contribution of cocaethylene to the enhanced effects produced by the co-administration of cocaine and alcohol was discussed.