Alcoholism is a tremendous health and financial burden on our society. A growing literature indicates that a series of interconnected brain regions referred to as the extended amygdala plays a key role in alcohol-related behaviors. In isolated studies, we and others have identified adaptations that occur at synapses in these regions in response to acute and chronic ethanol exposure. Here, we propose experiments to in parallel examine key points in this circuitry for their responses to a common alcohol treatment regimen, to better determine the concerted effects of ethanol and ethanol withdrawal. Moreover, we will assess molecular mechanisms involved in these actions through the use of a new conditional knockout mouse for the NMDA receptor subunit NR2B combined with a viral-directed knockout strategy. In total, the proposed work will begin to define specific mechanisms likely to play key roles in pathological adaptations and behaviors associated with chronic alcohol intake, thus providing new potential opportunities for therapeutic development.

Public Health Relevance

Alcoholism poses an enormous health and financial burden on our society. Currently, our understanding of the brain circuitries involved in alcoholism is far from complete. The successful completion of these proposed studies will result in important new information about neurons that may be involved in alcoholism, potentially creating new targets for therapeutics development.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA019455-03
Application #
8265728
Study Section
Neurotoxicology and Alcohol Study Section (NAL)
Program Officer
Cui, Changhai
Project Start
2010-07-01
Project End
2015-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
3
Fiscal Year
2012
Total Cost
$356,125
Indirect Cost
$127,840
Name
Vanderbilt University Medical Center
Department
Physiology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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