C 2/3: Stress-CIE Drinking Mouse Core

Marcelo Lopez

PROJECT SUMMARY
While the effect of stress on ethanol consumption has been extensively studied in several animal models, these studies have generally yielded equivocal findings, with results dependent on a number of factors including the type of stressor used, timing of stress presentation, and initial ethanol preference. During the current funding period, work conducted in this Core has focused on examining the interaction of stress with drinking in a model of dependence that involves repeated cycles of chronic intermittent ethanol (CIE) exposure. Studies demonstrated that repeated brief forced swim stress (FSS) exposure administered prior to ethanol drinking sessions produced a significant increase in ethanol drinking in CIE-exposed mice, but did not alter ethanol intake in nondependent mice. This reliable and robust FSS-induced selective enhancement of drinking in dependent mice produced a nearly 3-fold increase in blood ethanol levels. Interestingly, other stress procedures (e.g., restraint, foot-shock, social defeat) did not produce this effect, suggesting that FSS interacts with CIE exposure in a unique manner to promote further increases in ethanol drinking. Thus, this CIE-FSS drinking model is ideally suited to evaluate potential medications that may not only reduce excessive dependence-related drinking, but also temper the ability of stress to further enhance this elevated drinking. Accordingly, a major function of this Stress-CIE Drinking Mouse Core is to utilize the CIE-FSS Drinking model as a behavioral platform to evaluate medication effects on ethanol consumption in male and female dependent and nondependent mice. Medications selected for evaluation are based on their purported ability to target anti- stress and neuroinflammatory processes implicated in excessive alcohol consumption, thereby enabling the Core to provide service to the translational objectives of research projects in the INIAstress and INIAneuroimmune Consortia. Another function of the Core is to distribute brain tissue samples to INIA investigators to facilitate more comprehensive genomic and neural investigations in relation to the model. This, in turn, will facilitate new discoveries of potential novel targets and treatment strategies that can be tested in this Core. Taken together, the proposed research plan for the Stress-CIE Drinking Mouse Core will provide valuable service to the INIAstress and INIAneuroimmune Consortia, as well as the general alcohol research field. The overall goal of the Stress-CIE Drinking Mouse Core is to facilitate and aid in the identification and development of new treatment approaches for reducing stress-related excessive drinking and, more broadly, alcohol use disorders.