Stress-alcohol interactions clearly contribute to consequences of alcohol abuse, including increased anxiety during withdrawal from chronic exposure. However, little is known about the biological basis for these complex relationships. Animal models are likely to make significant contributions to our understanding of these issues. For example, comparisons between genetically-defined inbred mouse strains would provide a unique opportunity to understand the relevant genetic mechanisms regulating adaptations to chronic ethanol and withdrawal. Likewise, subjecting these strains to defined environmental stressors would yield important insight into the 'experience-dependent' mechanisms that influence the behavioral consequences (e.g. anxiety) related to this alcohol exposure. Although numerous brain regions are known to govern fear/anxiety behaviors, the lateral/basolateral amygdala is a central component of 'anxiety' circuitry. Because amygdale GABAA receptors regulate anxiety behavior, ethanol- and stress-dependent adaptations in this system may be important for the behavioral consequences related to their interactions. Our preliminary results suggest that the C57BL/6 (B6) and DBA/2J (D2) inbred mouse lines differ markedly in their basal anxiety as well as the functional and molecular expression of GABAA receptors expressed in lateral/basolateral amygdale (BLA). Preliminary findings also indicate that chronic ethanol exposure differentially alters the function of BLA GABAA receptors expressed by B6 and D2 neurons. Therefore, this application will specifically test the central hypothesis that lateral/basolateral amygdala GABAA receptor expression/function is a phenotypic marker for BLA GABAA the relative anxiety-related liability of stress-alcohol interactions. We will test our central hypothesis using housing manipulations and chronic ethanol inhalation to investigate the interactions between environmental stressors, amygdala GABAergic expression/function, and the neurobiological consequences of withdrawal. We will specifically integrate behavioral, molecular biological, and electrophysiological experimental approaches to better understand the stress-ethanol interactions related to anxiety-like behaviors. Ultimately, we hope our approach will allow us to eventually characterize the specific genetic mechanisms regulating the molecular and neurophysiological adaptations associated with these relationships. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01AA016671-02S1
Application #
7688881
Study Section
Special Emphasis Panel (ZAA1-DD (71))
Program Officer
Greenwell, Thomas
Project Start
2007-02-05
Project End
2010-01-31
Budget Start
2008-09-20
Budget End
2009-01-31
Support Year
2
Fiscal Year
2008
Total Cost
$18,007
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Physiology
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
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McCool, Brian A; Chappell, Ann M (2012) Using monosodium glutamate to initiate ethanol self-administration in inbred mouse strains. Addict Biol 17:121-31
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