A core criterion used to diagnose alcohol use disorders is the continued consumption of alcohol in the face of negative consequences. These consequences may include negative impact on work productivity, health, and interpersonal relationships. Preclinical animal models have been developed to study this and other behaviors that are observed in patients with addictive disorders. To study consumption despite negative consequences, the model of aversion-resistant alcohol intake has been developed. In this procedure, alcohol access is paired with a negative stimulus, usually either footshock punishment or quinine adulteration (a bitter tastant that rodents find highly aversive). The quinine adulteration model has been used in the last several years to examine the pharmacology and neurocircuitry of aversion resistant alcohol intake. However, the vast majority of these studies used male mice only. Our recent studies suggest that female mice show decreased sensitivity to quinine adulteration, suggesting that they are more aversion-resistant than male mice and may have a higher propensity for compulsive-like alcohol intake. This proposal examines this sex difference, first determining the role of circulating sex hormones in this behavioral phenotype and then examining the specific brain regions that mediate this effect. Examination of addiction-related behaviors using female subjects is of critical importance as we know far less about these processes in females due to the fact that studies in addiction biology have primarily used male animals. The outcomes of these experiments will help to further our understanding of the mechanisms that contribute to alcohol abuse in females and will open new avenues for medications development.

Public Health Relevance

A core criterion for alcoholism is the continued consumption of alcohol in the face of negative consequences. In animal models, aversive stimuli are paired with alcohol access to determine if mice will exhibit aversion-resistant alcohol consumption, which is thought to model the criterion for alcoholism described above. In the examination of this behavior, the vast majority of studies to this point have used only male animals and it is critical to understand the mechanisms involved in regulating this behavior in female subjects, and if any sex differences in this behavior exist.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Small Research Grants (R03)
Project #
1R03AA026989-01A1
Application #
9669527
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Grakalic, Ivana
Project Start
2020-01-03
Project End
2021-12-31
Budget Start
2020-01-03
Budget End
2020-12-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Georgia
Department
Physiology
Type
Schools of Veterinary Medicine
DUNS #
004315578
City
Athens
State
GA
Country
United States
Zip Code
30602