The interaction of cocaine and alcohol on schedule-controlled responding

The co-administration of cocaine and alcohol yielded greater rate-suppressing effects on schedule-controlled responding than either drug alone and than the sum of the individual effects of cocaine and alcohol (Experiment 1), suggesting a synergistic interaction between the two drugs. Although the basis for this synergism is not known, it is possible that it is mediated by cocaethylene, a cocaine metabolite produced in the presence of alcohol. Specifically, the effects of cocaethylene, which are reported in other preparations to be similar to those of cocaine, may be summating with the effects of cocaine and/or alcohol to produce the enhanced effects. To test this possibility, cocaethylene was combined with cocaine and alcohol and their effects on schedule-controlled responding were assessed (Experiment 2). Cocaethylene alone suppressed responding in a dose-related manner. Further, the combinations of cocaethylene and cocaine and of cocaethylene and alcohol at doses which alone had little or no effect resulted in suppression of licking and the effects of these combinations were greater than the sum of the individual drug effects, indicating apparent synergistic interactions between these two combinations. Given these results, a more parsimonious interpretation for the enhanced effects of the cocaine/alcohol combination (as well as those of the cocaine/cocaethylene and alcohol/cocaethylene combinations) is that of dose additivity of the respective drugs. If so, the combinations of different doses of the same drug should produce similar effects as the combinations of different drugs. To assess this, various doses of cocaine, of alcohol and of cocaethylene were combined and their effects were examined (Experiment 3). The same drug combinations produced similar increased suppression in operant responding and similar shifts in the dose-response functions as the combinations of different drugs, indicating that dose additivity may underlie the enhanced effects of the various drug combinations. This conclusion is further supported by an isobolographic analysis, a direct method of assessing dose additivity. Taken together, these results suggest that the interaction of cocaine and alcohol on schedule-controlled responding is a function of dose additivity. Such a conclusion may have implications for the co-use of cocaine and alcohol.