Alcoholism is a tremendous health and financial burden on our society. A growing literature indicates that the extended amygdala plays a key role in stress-reward interactions that may mediate key behavioral responses to chronic alcohol exposure. We demonstrated that chronic intermittent alcohol exposure up regulates CRF receptor dependent augmentation of glutamate release, as well as postsynaptic NMDA receptor function at extended amygdala glutamate synapses. We propose here to test a two-hit model, whereby affective disruptions produced by chronic alcohol exposure and withdrawal depend upon the coordinated pre- and postsynaptic regulation of extended amygdala glutamate synapses. We propose a series of experiments to map out mechanisms by which CRF receptor signaling regulates glutamate synapses, and to explore the alterations in NMDA receptor function that occur with alcohol exposure and withdrawal. We further propose to explore the impact of disruption of these processes on alcohol-abstinence induced depressive behaviors.

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 would 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
Method to Extend Research in Time (MERIT) Award (R37)
Project #
4R37AA019455-11
Application #
10209217
Study Section
Neurotoxicology and Alcohol Study Section (NAL)
Program Officer
Cui, Changhai
Project Start
2010-04-01
Project End
2025-07-31
Budget Start
2020-08-20
Budget End
2021-07-31
Support Year
11
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Physiology
Type
Schools of Medicine
DUNS #
965717143
City
Nashville
State
TN
Country
United States
Zip Code
37203
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