The goal of the proposed studies is to establish the behavioral correlates of cocaine administration and cocaine withdrawal in zebrafish. The central hypothesis of this proposal is that neurobiological mechanisms of drug reward and drug addiction in lower vertebrates are similar to those in mammals and that investigating them in zebrafish, a lower diurnal vertebrate with well-characterized genetics, would lead to a better understanding of addictive disorders and the development of more effective treatment strategies. This requires a detailed characterization of species-specific responses to cocaine in zebrafish and the evaluation of methodological approaches applicable to large-scale screening procedures. The proposed studies will be accomplished by conducting: i) automatic recordings of zebrafish locomotor activity and conditioned place preference, using digital image analysis system; and ii) high-speed digital imaging of swimming and turning patterns in larval zebrafish. These techniques will allow us to: a) Characterize the effects of cocaine treatment and cocaine withdrawal on locomotor activity and its circadian pattern in larval zebrafish; b) Establish whether zebrafish larvae develops behavioral sensitization to cocaine; c) Determine whether zebrafish larvae develops place preference to cocaine; d) Characterize the effects of cocaine treatment and cocaine withdrawal on specific locomotor patterns, e.g., swimming and turning; e) Determine whether melatonin treatment can modulate cocaine-induced changes in zebrafish behavior. A detailed characterization of the behavioral responses to cocaine in larval zebrafish would create a necessary foundation for intensive studies on the molecular and neuronal mechanisms of drug addiction, using multiple mutant phenotypes and transgenic zebrafish available. This could advance our understanding of the neuronal and intracellular targets of addictive substances and the genetic bases of vulnerability to drug addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA015418-02
Application #
6725309
Study Section
Biobehavioral and Behavioral Processes 3 (BBBP)
Program Officer
Volman, Susan
Project Start
2003-04-01
Project End
2006-03-30
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
2
Fiscal Year
2004
Total Cost
$242,250
Indirect Cost
Name
Boston University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
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Zhdanova, Irina V (2011) Sleep and its regulation in zebrafish. Rev Neurosci 22:27-36
Lopez Patino, Marcos A; Yu, Lili; Yamamoto, Bryan K et al. (2008) Gender differences in zebrafish responses to cocaine withdrawal. Physiol Behav 95:36-47
Lopez-Patino, Marcos A; Yu, Lili; Cabral, Howard et al. (2008) Anxiogenic effects of cocaine withdrawal in zebrafish. Physiol Behav 93:160-71
Shang, Eva H; Zhdanova, Irina V (2007) The circadian system is a target and modulator of prenatal cocaine effects. PLoS One 2:e587