Modeling drug addiction in females: how internal state and environmental context facilitate vulnerability

A fundamental aspect of survival is the ability to refine behaviors based on internal and external contexts. Interpretation of rewarding stimuli is driven by integration of a diverse number of inputs including contextual cues, hormone levels, and perceived valence of potentially stressful stimuli. These factors can influence the way that an organism makes decisions in the short term and how information is learned and stored on a longer time scale. With respect to addiction vulnerability, the interaction between context, dopamine, and drugs is particularly important. Historically, a majority of addiction research has focused on male subjects; however, a growing body of evidence has demonstrated that sex chromosome and hormonal differences between males and females can acutely influence the pharmacodynamic properties of drugs as well as the way information about cues and drugs are stored and encoded within the brain. Here we present considerations for how contextual information such as stress and social hierarchy can differentially affect males and females. This review presents a framework in which these contextual factors can be addressed and incorporated in our conceptualization of animal models of substance use disorders.