Alcohol addiction is a widespread problem in our society, yet initial exposure to alcohol does not universally result in addiction. The likely reason for this is varying levels of activity of an endogenous homeostatic mechanism which, when activated by alcohol consumption, reduces further consumption and thus prevents the development of addictive behaviors. The proposed research aims to further elucidate such a homeostatic pathway. Ethanol consumption triggers production of brain-derived neurotrophic factor (BDNF), and reduction of BDNF levels results in higher ethanol consumption. However, the downstream effectors of this ethanol-induced BDNF increase have not been determined. The proposed research will investigate the role of dynorphin, a protein which BDNF signaling can upregulate. First, the molecular connection between ethanol treatment and dynorphin production will be established. The link to ethanol-induced BDNF will be demonstrated both cellularly and behaviorally, by comparing wild type mice to conditional BDNF knockout mice. Finally, the proposed research will investigate the specific brain region in which this homeostasis occurs. These studies will increase our understanding of a brain mechanism for curbing alcohol addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31AA015462-01
Application #
6885203
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
$25,374
Indirect Cost
Name
Ernest Gallo Clinic and Research Center
Department
Type
DUNS #
173995366
City
Emeryville
State
CA
Country
United States
Zip Code
94608
Logrip, Marian L; Janak, Patricia H; Ron, Dorit (2009) Blockade of ethanol reward by the kappa opioid receptor agonist U50,488H. Alcohol 43:359-65
Logrip, Marian L; Janak, Patricia H; Ron, Dorit (2009) Escalating ethanol intake is associated with altered corticostriatal BDNF expression. J Neurochem 109:1459-68
Logrip, Marian L; Janak, Patricia H; Ron, Dorit (2008) Dynorphin is a downstream effector of striatal BDNF regulation of ethanol intake. FASEB J 22:2393-404
Janak, Patricia H; Wolf, Fred W; Heberlein, Ulrike et al. (2006) BIG news in alcohol addiction: new findings on growth factor pathways BDNF, insulin, and GDNF. Alcohol Clin Exp Res 30:214-21