Stress and gonadal steroid influences on alcohol drinking and withdrawal, with focus on animal models in females

Sexually dimorphic effects of alcohol, following binge drinking, chronic intoxication, and withdrawal, are documented at the level of the transcriptome and in behavioral and physiological responses. The purpose of the current review is to update and to expand upon contributions of the endocrine system to alcohol drinking and withdrawal in females, with a focus on animal models. Steroids important in the hypothalamic-pituitary–gonadal and hypothalamic–pituitary–adrenal axes, the reciprocal interactions between these axes, the effects of chronic alcohol use on steroid levels, and the genomic and rapid membrane-associated effects of steroids and neurosteroids in models of alcohol drinking and withdrawal are described. Importantly, comparison between males and females highlight some divergent effects of sex- and stress-steroids on alcohol drinking- and withdrawal-related behaviors, and the distinct differences in response emphasize the importance of considering sex in the development of novel pharmacotherapies for the treatment of alcohol use disorder.