Alcohol abuse is one of the most devastating and costly diseases society has to face. Its mechanisms are not well understood and effective treatment is lacking. One way to study this complex disease is with the use of model organisms. Zebrafish (Danio rerio) may be a useful model system with which the mechanisms of acute and chronic effects of alcohol can be investigated. Here new behavioral test paradigms will be developed for the quantification of alcohol effects on novelty induced, agonistic, social, and predator elicited behaviors. The tests are hoped to tap into diverse functions of the brain that may be modified by alcohol. The tests may enable us to detect a range of chemical mutagen induced genetic changes, a forward genetic approach. Zebrafish is particularly appropriate as a model organism for our purpose. First, it can be kept, bred, and tested in large numbers in the laboratory (small size, large number of offspring per spawning, ease of controlling environmental factors). Second, alcohol delivery is simple (fish absorb this substance through their gills and skin). Third, a large amount of genetic information and sophisticated genetic tools are available allowing the generation of mutations and identification of novel genes. And fourth, the genes discovered show high homology to human. Despite these advantages, however, phenotypical screening methods especially for behavior of zebrafish are often lacking. Importantly, we argue that the foundation of a successful forward genetic study lies in the development of appropriate phenotypical test paradigms. Furthermore, perhaps one of the best and simplest ways to test functional changes in the brain is behavioral analysis. Thus, the primary goal of this proposal is first to develop novel behavioral paradigms that detect alcohol induced changes, and second, to technically and procedurally refine these paradigms for high throughput screening of mutants. Another goal of this proposal is to generate and identify the first mutants with the use of the newly developed behavioral screens and then to establish stable mutant zebrafish lines. Ultimately, i.e. after the tenure of the proposal, the proposed studies will lead to the identification of novel genes relevant for alcohol related behaviors in zebrafish, which is hoped will facilitate the unraveling of the mechanisms of acute and chronic alcohol effects in human.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA015325-05
Application #
8099759
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Dunty, Jr, William
Project Start
2007-07-05
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
5
Fiscal Year
2011
Total Cost
$231,236
Indirect Cost
Name
University of Toronto
Department
Type
DUNS #
259999779
City
Toronto
State
ON
Country
Canada
Zip Code
M5 1-S8
Seguin, Diane; Shams, Soaleha; Gerlai, Robert (2016) Behavioral Responses to Novelty or to a Predator Stimulus Are Not Altered in Adult Zebrafish by Early Embryonic Alcohol Exposure. Alcohol Clin Exp Res 40:2667-2675
Luchiari, Ana C; Salajan, Diana C; Gerlai, Robert (2015) Acute and chronic alcohol administration: effects on performance of zebrafish in a latent learning task. Behav Brain Res 282:76-83
Tran, Steven; Chatterjee, Diptendu; Gerlai, Robert (2015) An integrative analysis of ethanol tolerance and withdrawal in zebrafish (Danio rerio). Behav Brain Res 276:161-70
Fernandes, Yohaan; Rampersad, Mindy; Gerlai, Robert (2015) Impairment of social behaviour persists two years after embryonic alcohol exposure in zebrafish: A model of fetal alcohol spectrum disorders. Behav Brain Res 292:102-8
Nowicki, Magda; Tran, Steven; Chatterjee, Diptendu et al. (2015) Inhibition of phosphorylated tyrosine hydroxylase attenuates ethanol-induced hyperactivity in adult zebrafish (Danio rerio). Pharmacol Biochem Behav 138:32-9
Stewart, A M; Ullmann, J F P; Norton, W H J et al. (2015) Molecular psychiatry of zebrafish. Mol Psychiatry 20:2-17
Tran, Steven; Gerlai, Robert (2015) Thirty-Second Net Stressor Task in Adult Zebrafish. Bio Protoc 5:
Tran, Steven; Gerlai, Robert (2014) Recent advances with a novel model organism: alcohol tolerance and sensitization in zebrafish (Danio rerio). Prog Neuropsychopharmacol Biol Psychiatry 55:87-93
Pannia, Emanuela; Tran, Steven; Rampersad, Mindy et al. (2014) Acute ethanol exposure induces behavioural differences in two zebrafish (Danio rerio) strains: a time course analysis. Behav Brain Res 259:174-85
Chatterjee, Diptendu; Shams, Soaleha; Gerlai, Robert (2014) Chronic and acute alcohol administration induced neurochemical changes in the brain: comparison of distinct zebrafish populations. Amino Acids 46:921-30

Showing the most recent 10 out of 42 publications