Associate Provost for Research Boston University Medical Campus
NIDA - National Institute on Drug Abuse	Research Resources

Abstract

Abstract: DESCRIPTION (provided by applicant): 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.

Thesaurus Terms:
behavioral habituation /sensitization, cocaine, drug addiction, drug withdrawal, larva, substance abuse related behavior
chordate locomotion, circadian rhythm, diving /swimming, embryo /fetus toxicology, ethology, immature animal, melatonin, phenotype, reinforcer
behavior test, behavioral /social science research tag, digital imaging, genetically modified animal, micromanipulator, statistics /biometry, zebrafish

Institution:	BOSTON UNIVERSITY MEDICAL CAMPUS
	715 ALBANY ST, 560
	BOSTON, MA 021182394
Fiscal Year:	2005
Department:	ANATOMY AND NEUROBIOLOGY
Project Start:	01-APR-2003
Project End:	31-MAR-2007
ICD:	NATIONAL INSTITUTE ON DRUG ABUSE
IRG:	BBBP