This is a chronological listing of grants held by this department, with the most recent listed first. New grants appear in this list weekly and contribute related to the department's Research Profile. The source of grants for this application comes directly from your institution.
Alcohol Induced Dysregulation of 5HT Signaling in the BNST
Thomas Kash4/1/2010 - 3/31/2012
|Sponsoring Organization:||Alcoholic Beverage Medical Research Foundation (ABMRF)|
|Awarding Organization Is:||University of North Carolina at Chapel Hill|
Thomas L. Kash (Lead Principal Investigator)
The goal of this proposal is to investigate the ability of alcohol exposure to regulate serotonin (5HT) signaling in the bed nucleus of the stria terminalis (BNST). A growing body of literature suggests that the negative affect, including anxiety-like behavior, associated with chronic alcohol use is due to a sensitization of stress systems within the brain. Numerous brain regions and neuromodulatory systems have been implicated in this process, including the BNST and 5HT system respectively. Consistent with this, preliminary data indicate that 5HT signaling in the BNST is altered by a chronic intermittent ethanol exposure. Further, 5HT signaling in the BNST can regulate anxiety like behavior. However, to date there has been no examination of the actions of 5HT on synaptic transmission in the BNST. Preliminary electrophysiological results show that 5HT signaling enhances inhibitory synaptic transmission in the BNST. Taken together, these data suggest a mechanism by which 5HT may alter function in the BNST and regulate anxiety-like behavior. Experiments in Aim 1 will explore the 5HT receptor and mechanism that underlie this modulatory action. The results from these experiments will provide insight as to the role that 5HT signaling in BNST plays in regulation of anxiety like behavior, a critical determinate of alcohol use. Experiments in Aim 2 will focus on adaptations in 5HT signaling in the BNST following chronic ethanol exposure. These experiments will utlilize molecular and electrophysiological approaches to identify specific alterations that may contribute to increased anxiety-like behavior following chronic ethanol exposure. Given the critical role that these long lasting behavioral deficits are believed to play in alcohol abuse, understanding molecular mechanisms that underlie this process could lead to more effective therapeutic interventions.