There is strong comorbidity between alcohol use disorders and chronic stress and anxiety. Dysfunction within overlapping neural targets of alcohol and stress may facilitate the development of this comorbid phenotype. The locus coeruleus norepinephrine (LC-NE) system is sensitive to both alcohol and stress and plays an important role in cognitive and emotional regulation of behavior. Plasticity within LC-NE circuits after chronic stress and alcohol can produce feed-forward effects, elevating stress and anxiety via the HPA axis and decreasing cognitive control by disrupting prefrontal cortex (PFC) function. The consequence of this stress- cognition ?double-hit? is an increased need to drink and a decreased control over drinking. Our preliminary evidence demonstrates that chronic intermittent ethanol exposure in addition to repeated swim stress, disrupts PFC dependent cognition and increases excessive drinking more than either ethanol or stress alone. In these studies we will investigate the LC as a key target of stress/ethanol maladaptations and the potential for LC-NE targeted therapeutics to ameliorate stress/ethanol induced executive dysfunction, elevated anxiety, and excessive drinking. This project will provide new insights into the role of LC-NE dysfunction after chronic stress and alcohol. Our results will identify novel circuit changes underlying excessive alcohol consumption and the potential for NE targeted therapies in treating cognitive and emotional dysfunction in alcohol use disorders.

Public Health Relevance

Excessive drinking and stress induced drinking pose a major economic and health burden. This project will characterize key changes in brain function due to stress and alcohol interactions. Results from these studies may lead to new treatment strategies for alcoholism that mitigate the effects of stress on drinking.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AA025481-04
Application #
9858163
Study Section
Special Emphasis Panel (ZAA1)
Program Officer
Liu, Qi-Ying
Project Start
2017-02-01
Project End
2022-01-31
Budget Start
2020-02-01
Budget End
2021-01-31
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Massachusetts Amherst
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
153926712
City
Hadley
State
MA
Country
United States
Zip Code
Moorman, David E (2018) The hypocretin/orexin system as a target for excessive motivation in alcohol use disorders. Psychopharmacology (Berl) 235:1663-1680
Vazey, Elena M; den Hartog, Carolina R; Moorman, David E (2018) Central Noradrenergic Interactions with Alcohol and Regulation of Alcohol-Related Behaviors. Handb Exp Pharmacol :
Moorman, David E (2018) The role of the orbitofrontal cortex in alcohol use, abuse, and dependence. Prog Neuropsychopharmacol Biol Psychiatry 87:85-107
Anderson, Rachel I; Moorman, David E; Becker, Howard C (2018) Contribution of Dynorphin and Orexin Neuropeptide Systems to the Motivational Effects of Alcohol. Handb Exp Pharmacol :
Rodberg, Ellen M; den Hartog, Carolina R; Anderson, Rachel I et al. (2017) Stress Facilitates the Development of Cognitive Dysfunction After Chronic Ethanol Exposure. Alcohol Clin Exp Res 41:1574-1583