Epidemiological data suggest that 50--90% of cocaine users choose to co-administer ethanol during binges. This thesis proposes that these statistics stem not from an enhanced reward produced by the additive effects of the two drugs, but rather, that ethanol serves to attenuate the delayed negative side-effects of cocaine administration. In the introductory chapter, three theories are described to account for the co-administration of cocaine and ethanol: negative reinforcement theory, positive reinforcement theory and the opponent-process theory. The first experiment, described in Chapter 2, revealed that animals consuming oral ethanol soon after traversing a straight alley for daily intravenous cocaine injections behaved in a manner suggestive that the drug acts to reduce post-cocaine anxiety. Chapter 3 discusses our use of the conditioned place preference method to determine whether a cocaine metabolite that is formed only in the presence of ethanol, cocaethylene, might some how account for the alcohol + cocaine results. In Chapter 4, we determined that rats, like humans, voluntarily chose to consume alcohol if they've been pretreated with cocaine. Only very low levels of cocaethylene were produced in subjects administered both cocaine and ethanol, indicating that this metabolite probably did not influence the behavior of subjects in the first two studies. The final study (Chapter 5) found that oral ethanol ameliorated the place aversion normally produced for an environment paired with the effects of intravenous cocaine present 15 minutes post-injection. However, this may be explained by the alteration in cocaine metabolism that occurs after ethanol pre-exposure. Combined, the results of these experiments suggest that the motivation of subjects to combine cocaine and ethanol largely stems from the ability of ethanol to reduce the negative/anxiogenic component of the cocaine experience.
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