PUBLICATION
Gene expression changes in a zebrafish model of drug dependency suggest conservation of neuro-adaptation pathways
- Authors
- Kily, L.J., Cowe, Y.C., Hussain, O., Patel, S., McElwaine, S., Cotter, F.E., and Brennan, C.H.
- ID
- ZDB-PUB-080506-14
- Date
- 2008
- Source
- The Journal of experimental biology 211(Pt 10): 1623-1634 (Journal)
- Registered Authors
- Brennan, Caroline
- Keywords
- nicotine, alcohol, conditioned place preference, drug dependency, zebrafish, gene expression
- MeSH Terms
-
- Analysis of Variance
- Animals
- Chemotaxis/drug effects*
- DNA Primers/genetics
- Ethanol/toxicity
- Gene Expression Regulation/drug effects*
- Nicotine/toxicity
- Oligonucleotide Array Sequence Analysis
- Reinforcement, Psychology*
- Reverse Transcriptase Polymerase Chain Reaction
- Reward*
- Substance-Related Disorders/metabolism*
- Zebrafish
- PubMed
- 18456890 Full text @ J. Exp. Biol.
Citation
Kily, L.J., Cowe, Y.C., Hussain, O., Patel, S., McElwaine, S., Cotter, F.E., and Brennan, C.H. (2008) Gene expression changes in a zebrafish model of drug dependency suggest conservation of neuro-adaptation pathways. The Journal of experimental biology. 211(Pt 10):1623-1634.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping