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E-GEOD-28527 - Transcriptome of globus pallidus from a mouse having a low score of cocaine-dependent conditioned place preference

Status
Released on 10 May 2015, last updated on 1 June 2015
Organism
Mus musculus
Samples (8)
Array (1)
Protocols (7)
Description
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. Agilent Whole Mouse Genome oligomicroarrays (GEO accession no. GPL4134, Agilent Technologies, Palo Alto, CA) were used. They contain 60-mer DNA probes synthesized in situ in a 44k format. Four independent (globus pallidus from mouse treated with cocaine and having a low score of conditioned place preference compared to globus pallidus from mouse treated with saline solution) hybridizations were carried out for each group of biological conditions using exchanged dye-labeled RNA targets (i.e., Cy3 and Cy5 dyeswapping experiments).
Experiment type
transcription profiling by array 
Contacts
Gilles Maussion <geo@ncbi.nlm.nih.gov>, Aude-Marie Lepagnol-Bestel, Evangelos Chortis, Florence Noble, Jean-Marie Moalic, Michel Simonneau, Philip Gorwood, Sabah Kelai, Sandrine Imbeaud
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-28527.idf.txt
Sample and data relationshipE-GEOD-28527.sdrf.txt
Raw data (1)E-GEOD-28527.raw.1.zip
Processed data (1)E-GEOD-28527.processed.1.zip
Array designA-MEXP-724.adf.txt
Links