Impact of Sex and Gonadal Hormones on Cocaine and Food Reinforcement Paradigms

Abstract

Men and women express sexually dimorphic patterns of cocaine abuse, such that women progress faster from initially trying cocaine to becoming dependent upon the drug and display a greater incidence of relapse. Sex differences in response to cocaine are also seen in the laboratory in both humans and animal models. In this review, animal models of cocaine abuse that have reported sex differences in appetitive reinforcement are discussed. In both human and animal studies, sex differences in the subjective and behavioral effects of cocaine are often related to the female reproductive cycle and ovarian hormones. As a comparison, food reinforcement studies have shown the opposite profile of sex differences and the impact of sex steroids on food intake and response rate. In contrast, limited attention has been given to "choice" models in rodents of either sex, however, our recent studies have indicated a role of sex and estrogen in cocaine choice over food with intact females, and OVX females treated with estrogen, choosing cocaine significantly more than males. Interestingly, estrous cycle phase does not seem to impact cocaine choice as it does response rate in single-reinforcer studies, suggesting that genomic rather than neurosteroid effects of estrogen modulate sex differences in this model. Future studies should more fully explore the impact of sex hormones on concurrent reinforcement and discrete choice models of addiction.