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.

Public Health Relevance

While stress is known to be a significant factor that contributes to heavy and hazardous alcohol drinking, few treatments are available to reduce stress-related excessive alcohol intake. This Core serves a central supportive function for INIA-related research projects by providing valuable information regarding medications that can reduce the ability of stress to promote excessive alcohol consumption. The goal is to identify new treatment approaches for reducing stress-related excessive drinking and, more broadly, alcohol use disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Resource-Related Research Projects--Cooperative Agreements (U24)
Project #
5U24AA020929-08
Application #
9631407
Study Section
Special Emphasis Panel (ZAA1)
Program Officer
Regunathan, Soundar
Project Start
2012-02-10
Project End
2022-01-31
Budget Start
2019-02-01
Budget End
2020-01-31
Support Year
8
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Medical University of South Carolina
Department
Psychiatry
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29403
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Haun, Harold L; Griffin, William C; Lopez, Marcelo F et al. (2018) Increasing Brain-Derived Neurotrophic Factor (BDNF) in medial prefrontal cortex selectively reduces excessive drinking in ethanol dependent mice. Neuropharmacology 140:35-42
Farris, Sean P; Riley, Brien P; Williams, Robert W et al. (2018) Cross-species molecular dissection across alcohol behavioral domains. Alcohol 72:19-31
Nimitvilai, Sudarat; Lopez, Marcelo F; Woodward, John J (2018) Effects of monoamines on the intrinsic excitability of lateral orbitofrontal cortex neurons in alcohol-dependent and non-dependent female mice. Neuropharmacology 137:1-12
Lopez, Marcelo F; Miles, Michael F; Williams, Robert W et al. (2017) Variable effects of chronic intermittent ethanol exposure on ethanol drinking in a genetically diverse mouse cohort. Alcohol 58:73-82
Becker, Howard C (2017) Influence of stress associated with chronic alcohol exposure on drinking. Neuropharmacology 122:115-126
Porcu, Patrizia; O'Buckley, Todd K; Lopez, Marcelo F et al. (2017) Initial genetic dissection of serum neuroactive steroids following chronic intermittent ethanol across BXD mouse strains. Alcohol 58:107-125
van der Vaart, Andrew D; Wolstenholme, Jennifer T; Smith, Maren L et al. (2017) The allostatic impact of chronic ethanol on gene expression: A genetic analysis of chronic intermittent ethanol treatment in the BXD cohort. Alcohol 58:93-106
Siciliano, Cody A; Locke, Jason L; Mathews, Tiffany A et al. (2017) Dopamine synthesis in alcohol drinking-prone and -resistant mouse strains. Alcohol 58:25-32
Anderson, Rachel I; Becker, Howard C (2017) Role of the Dynorphin/Kappa Opioid Receptor System in the Motivational Effects of Ethanol. Alcohol Clin Exp Res 41:1402-1418

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