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ZFIN ID: ZDB-PUB-060616-44
D4 Dopamine receptor genes of zebrafish and effects of the antipsychotic clozapine on larval swimming behaviour
Boehmler, W., Carr, T., Thisse, C., Thisse, B., Canfield, V.A., and Levenson, R.
Date: 2007
Source: Genes, brain, and behavior 6(2): 155-166 (Journal)
Registered Authors: Boehmler, Wendy, Canfield, Victor, Levenson, Robert, Thisse, Bernard, Thisse, Christine
Keywords: none
MeSH Terms:
  • Amino Acid Sequence
  • Analysis of Variance
  • Animals
  • Chromosome Mapping
  • Clozapine/pharmacology*
  • Dopamine Antagonists/pharmacology*
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Developmental
  • Gene Library
  • Larva/drug effects
  • Molecular Sequence Data
  • Motor Activity/drug effects*
  • Motor Activity/genetics
  • Receptors, Dopamine D4/drug effects*
  • Receptors, Dopamine D4/genetics
  • Receptors, Dopamine D4/metabolism
  • Sequence Homology, Amino Acid
  • Swimming
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Zebrafish Proteins/drug effects*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 16764679 Full text @ Genes Brain Behav.
FIGURES
ABSTRACT
Zebrafish, a model developmental genetic organism, is being increasingly used in behavioural studies. We have initiated studies designed to evaluate the response of zebrafish to antipsychotic drugs. This study focuses on characterization of zebrafish D4 dopamine receptors (D4Rs) and the response of larval zebrafish to the atypical antipsychotic clozapine. The D4R is of interest because of its high affinity for clozapine, while interest in clozapine stems from its effectiveness in reducing symptoms in acutely psychotic, treatment-resistant schizophrenic patients. By mining the zebrafish genomic database, we identified three distinct D4R genes, drd4a, drd4b and drd4c, and generated full-length open reading frames encoding each of the three D4Rs by reverse transcription-polymerase chain reaction. Gene mapping studies showed that each D4R gene mapped to a distinct chromosomal location in the zebrafish genome, and each gene exhibited a unique expression profile during embryogenesis. When administered to larval zebrafish, clozapine produced a rapid and profound effect on locomotor activity. The effect of clozapine was dose-dependent, resulted in hypoactivity and was prevented by the D4-selective agonist ABT-724. Our data suggest that the inhibitory effect of clozapine on the locomotor activity of larval zebrafish may be mediated through D4Rs.
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