Gene expression changes in a zebrafish model of drug dependency suggest conservation of neuro-adaptation pathways
2008
SUMMARY Addiction is a complex psychiatric disorder considered to be a disease of
the brain9s natural reward reinforcement system. Repeated stimulation of the
`reward9 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.
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