Alcoholism and alcohol abuse are major health problems and represent a tremendous financial burden on our society. A growing literature indicates that chronic alcohol exposure leads to an imbalance between central stress and anti-stress systems in key brain circuits that regulate emotional behavior. These imbalances can lead to pathological behavior, including increased anxiety, stress-responsivity and enhanced risk of relapse. Despite these advances identifying the role these systems play in alcohol related behaviors, there remains a gap in our knowledge of the fundamental biological, cellular and circuit mechanisms that contribute to this dysregulated behavior. In order to more effectively treat alcohol abuse, it is necessary to define the impact of chronic alcohol exposure on the in the circuitry that is critical for regulation of this behavior. Here, we propose to characterize the impact of chronic alcohol exposure on anti-stress systems, specifically neuropeptide Y (NPY) and GABAergic neuroactive steroids, in the amygdala and extended amygdala, brain regions critical for regulation of stress and anxiety-like behavior. Additionally, we will utilize inducible channel rhodopsin viruses in combination with neurochemically specific Cre-recombinase driver lines to determine the impact of chronic alcohol exposure on GABAergic circuits in these brain regions. In total, the proposed work will begin to define specific alcohol-induced cellular and circuit adaptations that are likely to play key roles in pathological behaviors associated with alcoholism.

Public Health Relevance

The focus of this project is to understand how alcohol exposure alters emotional behavior. Successful completion of this project will result in a greater understanding of how alcohol changes brain function. Further, these studies may provide insight as to how to develop more useful treatments for alcoholism and anxiety disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AA020911-02
Application #
8423705
Study Section
Special Emphasis Panel (ZAA1-DD (51))
Program Officer
Liu, Qi-Ying
Project Start
2012-02-10
Project End
2017-01-31
Budget Start
2013-02-01
Budget End
2014-01-31
Support Year
2
Fiscal Year
2013
Total Cost
$172,050
Indirect Cost
$55,800
Name
University of North Carolina Chapel Hill
Department
Pharmacology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Crowley, Nicole A; Bloodgood, Daniel W; Hardaway, J Andrew et al. (2016) Dynorphin Controls the Gain of an Amygdalar Anxiety Circuit. Cell Rep 14:2774-83
Pleil, Kristen E; Helms, Christa M; Sobus, Jon R et al. (2016) Effects of chronic alcohol consumption on neuronal function in the non-human primate BNST. Addict Biol 21:1151-1167
Vardy, Eyal; Robinson, J Elliott; Li, Chia et al. (2015) A New DREADD Facilitates the Multiplexed Chemogenetic Interrogation of Behavior. Neuron 86:936-46
Kash, Thomas L; Pleil, Kristen E; Marcinkiewcz, Catherine A et al. (2015) Neuropeptide regulation of signaling and behavior in the BNST. Mol Cells 38:1-13
Radke, Anna K; Jury, Nicholas J; Kocharian, Adrina et al. (2015) Chronic EtOH effects on putative measures of compulsive behavior in mice. Addict Biol :
Lowery-Gionta, Emily G; Marcinkiewcz, Catherine A; Kash, Thomas L (2015) Functional alterations in the dorsal raphe nucleus following acute and chronic ethanol exposure. Neuropsychopharmacology 40:590-600
Lovinger, David M; Kash, Thomas L (2015) Mechanisms of Neuroplasticity and Ethanol's Effects on Plasticity in the Striatum and Bed Nucleus of the Stria Terminalis. Alcohol Res 37:109-24
Hardaway, J A; Crowley, N A; Bulik, C M et al. (2015) Integrated circuits and molecular components for stress and feeding: implications for eating disorders. Genes Brain Behav 14:85-97
Pleil, Kristen E; Lowery-Gionta, Emily G; Crowley, Nicole A et al. (2015) Effects of chronic ethanol exposure on neuronal function in the prefrontal cortex and extended amygdala. Neuropharmacology 99:735-49
Crowley, Nicole A; Kash, Thomas L (2015) Kappa opioid receptor signaling in the brain: Circuitry and implications for treatment. Prog Neuropsychopharmacol Biol Psychiatry 62:51-60

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