Differences in sensitivity to ethanol?s aversive effects during initial use are an important contributing risk factor for ethanol abuse in future. Individuals who show a low aversive response e.g. slurring of speech and motor incoordination during initial ethanol use are more at risk to start excessive drinking in future and to develop alcohol use disorder (AUD). Lateral Habenula (LHb) is a brain area that is involved in learning through aversive outcomes and thus ethanol induced LHb activity during initial ethanol use can likely play a role in modulating ethanol intake. Furthermore, there is a strong correlation between negative emotional state and subsequent alcohol intake and thus development of AUD over time. Also, in both human and rodent studies, negative emotional state is associated with higher LHb activity. These result suggests that both baseline and ethanol induced LHb activity could contribute to modulation of future ethanol consumption. Wistar rats and selectively bred alcohol-preferring (P) show significant differences in average ethanol intake and P rats are a validated model for AUD. However, until now, the neural circuitry underlying these differences in ethanol consumption over time in the two groups of rats and the critical role of the LHb in this circuitry specifically has not been determined. Thus we will test whether differences in baseline LHb firing and LHb neuronal responses during early ethanol use determine future ethanol intake in ethanol naive P and Wistar rats.
For Aim 1, we will record the baseline LHb firing rate and the Ultrasonic vocalizations (USVs) in male and female ethanol nave P and Wistar rats. We expect that P rats will show higher baseline LHb firing rates and more counts of 22-28 KHz USVs (aversive) calls as compared to Wistar rats.
For Aim 2, we will record the LHb firing rate and the USVs following ethanol injection in ethanol nave P and Wistar rats. We expect that P rats will show lower LHb firing following ethanol injection and fewer counts of aversive calls as compared to Wistar rats. Rats in both Aim 1 and 2 will then undergo an intermittent access 2-bottle choice paradigm for seven weeks to measure average and end point voluntary ethanol consumption.

Public Health Relevance

Affective state prior to ethanol use as well as difference in aversive effects of ethanol following initial use may modulate risk of alcohol abuse in future. We will test the role of differences in the activity of a brain area, Lateral Habenula, involved in aversive learning, in two strains of rats, prior to and during initial alcohol use in modulating future alcohol consumption.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Small Research Grants (R03)
Project #
1R03AA026758-01A1
Application #
9667989
Study Section
Neurotoxicology and Alcohol Study Section (NAL)
Program Officer
Egli, Mark
Project Start
2018-12-10
Project End
2020-11-30
Budget Start
2018-12-10
Budget End
2020-11-30
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Utah
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112