| Alcohol withdrawal presents a significant challenge for the alcoholic individual, either for the distress (dysphoria) produced, or because of the risk for significant and potentially life-threatening seizures that may occur. The dysphoria also poses a risk for relapse to drinking in order to overcome the unpleasant symptoms of withdrawal experienced in early withdrawal. We have been interested in studying the role of sex in problems of alcoholism because studies show that women have an overall lower lifetime prevalence of alcoholism than men, but, women who abuse alcohol suffer more from its untoward consequences than men. However, alcoholic men endorse more withdrawal symptoms such as anxiety and insomnia, even when established gender differences in alcohol metabolism, drinking patterns and alcohol-related problems are taken into account. We have found significant sex-selective differences in the timing of recovery from ethanol withdrawal, as well as interesting sex differences in seizure latency and severity as indicators of ethanol withdrawal behaviors in male and female rats. We have also found remarkable sex differences in expression and activity of GABAergic and glutamatergic receptor systems during ethanol withdrawal. The overall goal of this project was to explore mechanisms involved in ethanol withdrawal behaviors at different timepoints (1 and 3 days) of withdrawal. We hypothesized that inherent sex differences in brain structure and function are involved in the differential expression of ethanol withdrawal events. Different hormonal environments between males and females, especially the differing levels of ovarian steroids and sexual dimorphism of male and female brains, impact the mechanisms that lead to the differential expression of ethanol withdrawal behaviors. Findings in young adult males, intact females and ovariectomized females were compared and contrasted to test the hypothesis. These studies elucidated some of the mechanisms that impart the different responses seen in male and female rats during ethanol withdrawal, and provide a basis for an improved understanding and rational treatment of alcohol dependence and withdrawal in men and women. |
