Relapse remains problematic for alcoholics due, in part to the lack of effective pharmacotherapies. Identification of the precise molecular entities that contribute to relapse may facilitate rational drug design. Recent findings indicate a role of molecules that modulate signaling through G-proteins in relapse. This proposal focuses on the Activator of G-protein Signaling (AGS3). AGS3 expression increases during withdrawal from repeated cocaine administration. High AGS3 expression appears to induce neurochemistry resembling that found in addicted animals and AGS3 expression appears to increase the propensity to relapse to cocaine seeking behavior. AGS3 expression also increases in vitro after repeated ethanol exposure and in vivo after withdrawal from repeated ethanol administration. The role of AGS3 in alcoholism, however, remains to be elucidated. This proposal will determine the role of AGS3 and its signaling partner Gbetagamma in both the genetic and behavioral impact of repeated ethanol administration. Our objective is to determine if AGS3 contributes to relapse to ethanol seeking behavior. Our findings may aid pharmaceutical development for individuals suffering from alcoholism and alcohol abuse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AA015464-01
Application #
6885628
Study Section
Special Emphasis Panel (ZAA1-EE (20))
Program Officer
Sorensen, Roger
Project Start
2005-01-16
Project End
2008-01-15
Budget Start
2005-01-16
Budget End
2006-01-15
Support Year
1
Fiscal Year
2005
Total Cost
$42,976
Indirect Cost
Name
Ernest Gallo Clinic and Research Center
Department
Type
DUNS #
173995366
City
Emeryville
State
CA
Country
United States
Zip Code
94608
Bowers, Michael Scott (2010) Activators of G-protein signaling 3: a drug addiction molecular gateway. Behav Pharmacol 21:500-13
Hopf, F Woodward; Bowers, M Scott; Chang, Shao-Ju et al. (2010) Reduced nucleus accumbens SK channel activity enhances alcohol seeking during abstinence. Neuron 65:682-94
Bowers, M Scott; Hopf, F Woodward; Chou, Jonathan K et al. (2008) Nucleus accumbens AGS3 expression drives ethanol seeking through G betagamma. Proc Natl Acad Sci U S A 105:12533-8