Abstract
In an attempt to understand polysubstance abuse, and because little research has been performed regarding cocaethylene and genetic traits, the overall goal of this study was to determine if the hepatically synthesized metabolite of concurrent cocaine and ethanol administration, cocaethylene (CE), would display a genetic predisposition in rodents to seek its rewarding effects. This overall goal was achieved by employing the behavioral paradigm of conditional place preference (CPP). Male rats who were shown to highly prefer the effect of cocaethylene were mated with preferring females; nonpreferring males were mated with nonpreferring females; and randomly selected rats from the lower ends of each group were also mated. Subjects were selectively bred based on their degree of place preference to cocaethylene administration. The rats were further tested for locomotor activation by the psychostimulant properties of cocaethylene and for discrimination of interoceptive cues by using the drug discrimination paradigm to determine if these behavioral traits were passed on with drug preference. The results of this series of experiments suggest that behavioral traits have a complex multigenic etiology. Despite the significant differences displayed between the subjects selectively bred to produce preferring and nonpreferring lines, there are multiple neuroanatomical circuits and neurochemical pathways involved in generating the apparent genetically different behaviors. Similar to the many studies demonstrating a probable genetic/ inheritable predisposition for alcoholism, non-ethanol abuse liability is probably controlled by many genes and gene products.