Repeated binge alcohol drinking is a major public health problem and is thought to lead to pathophysiological alterations in brain circuitry that contribute to alcohol dependence and addiction. While complex behaviors such as ethanol consumption are likely controlled by a distributed, interconnected network of brain nuclei, corticotropin releasing factor (CRF) producing neurons within the central nucleus of the amygdala (CeA) are thought to play a crucial role in progressively driving pathological ethanol consumption. The CeA is composed of numerous neurochemically distinct neurons, and therefore determining how endogenous CRF signaling modulates neural circuits via their functional connectivity with postsynaptic targets has proven difficult due to technical limitations in evaluating specific long-range synaptic projections. To circumvent this, we propose to use optogenetic techniques coupled with brain slice electrophysiology and behavioral assays to examine the properties of CRF neuronal circuits in the extended amygdala and to determine whether activation or inhibition of CRF containing neural circuit elements can alter binge ethanol intake. We hypothesize that CRF producing neurons within the CeA project to the bed nucleus of the stria terminalis (BNST), and that activation of this pathway will be enhanced and required for repeated binge ethanol intake. We will test this hypothesis using a multi-disiclplinary approach combining both in vivo and ex vivo analysis of function. In total, the proposed research will provide essential information concerning the role that the CRF projection from the CeA to the BNST plays in binge ethanol drinking.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Comprehensive Center (P60)
Project #
5P60AA011605-17
Application #
8593211
Study Section
Special Emphasis Panel (ZAA1-GG)
Project Start
Project End
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
17
Fiscal Year
2014
Total Cost
$203,150
Indirect Cost
$69,499
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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