Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Genome Biol. 2009;10(7):R81. doi: 10.1186/gb-2009-10-7-r81. Epub 2009 Jul 31.

Zebrafish reward mutants reveal novel transcripts mediating the behavioral effects of amphetamine.

Author information

  • 1Department Zebrafish Neurogenetics, Institute of Developmental Genetics, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Ingolstaedter Landstrasse, Neuherberg, 85764 Germany. katharine.webb@helmholtz-muenchen.de

Abstract

BACKGROUND:

Addiction is a pathological dysregulation of the brain's reward systems, determined by several complex genetic pathways. The conditioned place preference test provides an evaluation of the effects of drugs in animal models, allowing the investigation of substances at a biologically relevant level with respect to reward. Our lab has previously reported the development of a reliable conditioned place preference paradigm for zebrafish. Here, this test was used to isolate a dominant N-ethyl-N-nitrosourea (ENU)-induced mutant, no addiction (nad(dne3256)), which fails to respond to amphetamine, and which we used as an entry point towards identifying the behaviorally relevant transcriptional response to amphetamine.

RESULTS:

Through the combination of microarray experiments comparing the adult brain transcriptome of mutant and wild-type siblings under normal conditions, as well as their response to amphetamine, we identified genes that correlate with the mutants' altered conditioned place preference behavior. In addition to pathways classically involved in reward, this gene set shows a striking enrichment in transcription factor-encoding genes classically involved in brain development, which later appear to be re-used within the adult brain. We selected a subset of them for validation by quantitative PCR and in situ hybridization, revealing that specific brain areas responding to the drug through these transcription factors include domains of ongoing adult neurogenesis. Finally, network construction revealed functional connections between several of these genes.

CONCLUSIONS:

Together, our results identify a new network of coordinated gene regulation that influences or accompanies amphetamine-triggered conditioned place preference behavior and that may underlie the susceptibility to addiction.

Comment in

PMID:
19646228
[PubMed - indexed for MEDLINE]
PMCID:
PMC2728535
Free PMC Article

Images from this publication.See all images (7)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for BioMed Central Icon for PubMed Central
    Loading ...
    Write to the Help Desk