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First published online May 2, 2008
Journal of Experimental Biology 211, 1623-1634 (2008)
Published by The Company of Biologists 2008
doi: 10.1242/jeb.014399

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Gene expression changes in a zebrafish model of drug dependency suggest conservation of neuro-adaptation pathways

Layla J. M. Kily¹, Yuka C. M. Cowe¹, Osman Hussain¹, Salma Patel¹, Suzanne McElwaine², Finbarr E. Cotter² and Caroline H. Brennan^1,*

¹ School of Biological and Chemical Sciences, Queen Mary, University of London, Mile End, London E1 4NS, UK
² Centre for Haematology, Institute of Cell and Molecular Science, Barts & The London, Queen Mary's School of Medicine, 4 Newark Street, London E1 2AD, UK

^* Author for correspondence (e-mail: C.H.Brennan{at}qmul.ac.uk)

Accepted 11 March 2008

Addiction is a complex psychiatric disorder considered to be a disease of the brain's natural reward reinforcement system. Repeated stimulation of the `reward' pathway leads to adaptive changes in gene expression and synaptic organization that reinforce drug taking and underlie long-term changes in behaviour. The primitive nature of reward reinforcement pathways and the near universal ability of abused drugs to target the same system allow drug-associated reward and reinforcement to be studied in non-mammalian species. Zebrafish have proved to be a valuable model system for the study of vertebrate development and disease. Here we demonstrate that adult zebrafish show a dose-dependent acute conditioned place preference (CPP) reinforcement response to ethanol or nicotine. Repeated exposure of adult zebrafish to either nicotine or ethanol leads to a robust CPP response that persists following 3 weeks of abstinence and in the face of adverse stimuli, a behavioural indicator of the establishment of dependence. Microarray analysis using whole brain samples from drug-treated and control zebrafish identified 1362 genes that show a significant change in expression between control and treated individuals. Of these genes, 153 are common to both ethanol- and nicotine-treated animals. These genes include members of pathways and processes implicated in drug dependence in mammalian models, revealing conservation of neuro-adaptation pathways between zebrafish and mammals.

Key words: nicotine, alcohol, conditioned place preference, drug dependency, zebrafish, gene expression