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| Status |
Public on May 10, 2015 |
| Title |
Transcriptome of accumbens nuclei from mice having low scores of cocaine-dependent conditioned place preference |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Molecular basis of transition to addiction in vulnerable individuals is largely unknown. We hypothesized that human susceptibility genes can be identified on the basis of conserved molecular mechanisms in rodent brains. We used a short-term cocaine-dependent conditioned place preference (CPP) to identify genetic hallmarks of early steps of reward memory in basal ganglia including accumbens nucleus (NAc), globus pallidus (GP) and subthalamic nucleus (STN). Using genome-wide microarray analysis and CPP as a quantitative trait, we found that synaptic plasticity-related genes are deregulated in these three structures. A significant enrichment in bona fide transcripts involved in dendritic spine local translation was evidenced. mGluR5 is transcriptionally deregulated in Acc and GP of cocaine-treated animals. Grin3a that encodes a NMDA receptor subunit involved in Ca++ permeability is deregulated in NAc. Furthermore, Orexin/Hcrt transcript level is decreased in STN, a region known to be involved in discriminating addictive drugs and natural rewards. We also found that mGluR5 and Grin3a expression deregulation is sufficient to induce changes in synaptic plasticity-related genes. Altogether, these results suggest that a combined deregulation of mGluR5 and Grin3A pathway in NAc, mGluR5 in GP and orexin system in STN may generate an incentive memory contrasted between addictive drugs and natural rewards. Such pathways may include clusters of genes that are potential susceptibility genes for transition to addiction.
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| Overall design |
Agilent Whole Mouse Genome oligomicroarrays (GEO accession no. GPL2872, Agilent Technologies, Palo Alto, CA) were used. They contain 60-mer DNA probes synthesized in situ in a 44k format. Of 44,290 spots, 2756 are controls. The remaining 41,534 spots represent 33,661 unique transcripts which correspond to 20,202 unique human genes. Five independent (five accumbens nuclei from mice treated with cocaine and having a low score of conditioned place preference compared to five accumbens nuclei from mice treated with saline solution) measurements were carried out for each group of biological conditions using exchanged dye-labeled RNA targets (i.e., Cy3 and Cy5 dyeswapping experiments).
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| Contributor(s) |
Kelai S, Maussion G, Lepagnol-Bestel A, Chortis E, Imbeaud S, Noble F, Moalic J, Gorwood P, Simonneau M |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Apr 11, 2011 |
| Last update date |
May 10, 2015 |
| Contact name |
Gilles Maussion |
| Organization name |
INSERM U675
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| Street address |
16 rue Henri Huchard
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| City |
PARIS |
| ZIP/Postal code |
75018 |
| Country |
France |
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| Platforms (1) |
| GPL2872 |
Agilent-012694 Whole Mouse Genome G4122A (Feature Number version) |
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| Samples (5)
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| This SubSeries is part of SuperSeries: |
| GSE28828 |
Transcriptomes of subthalamic nuclei, globus pallidus, and accumbens nuclei from mice with low and high scores of cocaine-dependent conditioned place preference |
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| Relations |
| BioProject |
PRJNA143037 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE28529_RAW.tar |
21.8 Mb |
(http)(custom) |
TAR (of GPR) |
| Processed data included within Sample table |
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