The goal of this project is to carry out a systematic genetic analysis in the zebrafish Danio rerio, to understand the biological effects of alcohol on cell signaling. Understanding the molecular mechanisms that mediate cellular responses to acute or chronic ethanol treatment is not only important for understanding the complex signal transduction pathways and their cross regulation inside cells, but is also critical for understanding alcoholism, alcohol abuse, and the medical complications of excessive drinking. Simple and robust assays have been developed in zebrafish to assess the effects of acute as well as chronic alcohol exposure on cell signaling. By using these simple and powerful assays, we have carried out a pilot mutagenesis screen and identified mutations that display abnormal responses to either acute or chronic treatment of ethanol. These molecular genetic analyses will provide fundamental insights into signal transduction mechanisms and its modulation by acute and chronic alcohol exposure. Future behavioral and pathophysiological analyses can be done using the isolated zebrafish mutants. Further, molecules identified in zebrafish will provide candidate genes for association study of human alcoholism and alcoholic medical disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA016021-04
Application #
7648242
Study Section
Neurotoxicology and Alcohol Study Section (NAL)
Program Officer
Dunty, Jr, William
Project Start
2006-09-30
Project End
2011-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
4
Fiscal Year
2009
Total Cost
$337,544
Indirect Cost
Name
University of California San Francisco
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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Wagle, Mahendra; Mathur, Priya; Guo, Su (2011) Corticotropin-releasing factor critical for zebrafish camouflage behavior is regulated by light and sensitive to ethanol. J Neurosci 31:214-24
Mathur, Priya; Guo, Su (2011) Differences of acute versus chronic ethanol exposure on anxiety-like behavioral responses in zebrafish. Behav Brain Res 219:234-9
Lau, Billy Y B; Mathur, Priya; Gould, Georgianna G et al. (2011) Identification of a brain center whose activity discriminates a choice behavior in zebrafish. Proc Natl Acad Sci U S A 108:2581-6
Mathur, Priya; Lau, Billy; Guo, Su (2011) Conditioned place preference behavior in zebrafish. Nat Protoc 6:338-45
Mathur, Priya; Berberoglu, Michael A; Guo, Su (2011) Preference for ethanol in zebrafish following a single exposure. Behav Brain Res 217:128-33
Mathur, Priya; Guo, Su (2010) Use of zebrafish as a model to understand mechanisms of addiction and complex neurobehavioral phenotypes. Neurobiol Dis 40:66-72
Guo, Su (2009) Using zebrafish to assess the impact of drugs on neural development and function. Expert Opin Drug Discov 4:715-726
Peng, Jisong; Wagle, Mahendra; Mueller, Thomas et al. (2009) Ethanol-modulated camouflage response screen in zebrafish uncovers a novel role for cAMP and extracellular signal-regulated kinase signaling in behavioral sensitivity to ethanol. J Neurosci 29:8408-18
Mueller, Thomas; Guo, Su (2009) The distribution of GAD67-mRNA in the adult zebrafish (teleost) forebrain reveals a prosomeric pattern and suggests previously unidentified homologies to tetrapods. J Comp Neurol 516:553-68