Alcohol action on extended amygdala glutamate synapses

Vanderbilt University, Nashville TN

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Abstract

? DESCRIPTION (provided by applicant): 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.