The impact of sex, species, environmental context, and alternative reinforcers in animal models of cocaine use disorders.

Cocaine use disorder (CUD) remains a major public health challenge with no effective pharmacological treatments to date. Although extensive preclinical research using animal models has advanced our understanding, these findings have yet to translate into clinical success. This review highlights key independent variables that should be incorporated to improve the validity and translational relevance of animal studies. The discussion is organized around three primary domains: the agent; the host; and the environment. Most studies in this review focus on cocaine as the agent and host factors such as species and sex are emphasized as important independent variables influencing outcomes. The central theme of this review is to emphasize, from a preclinical model perspective, the critical role of environmental context, including operant conditioning parameters like schedules of reinforcement and maintaining events, as well as social housing conditions, which profoundly impact cocaine-maintained behavior and the effectiveness of interventions for cocaine self-administration.