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Series GSE43410 Query DataSets for GSE43410
Status Public on Jan 10, 2013
Title Effects of cocaine and withdrawal on the mouse nucleus accumbens transcriptome.
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Genetic association studies, pharmacological investigations and analysis of mice-lacking individual genes have made it clear that Cocaine administration and Withdrawal have a profound impact on multiple neurotransmitter systems. The GABAergic medium spiny neurons of the nucleus accumbens (NAc) exhibit changes in the expression of genes encoding receptors for glutamate and in the signaling pathways triggered by dopamine binding to G-protein-coupled dopamine receptors. Deep sequence analysis provides a sensitive, quantitative and global analysis of the effects of Cocaine on the NAc transcriptome. RNA prepared from the NAc of adult male mice receiving daily injections of Saline or Cocaine, or Cocaine followed by a period of Withdrawal, was used for high-throughput sequence analysis. Changes were validated by quantitative polymerase chain reaction or Western blot. On the basis of pathway analysis, a preponderance of the genes affected by Cocaine and Withdrawal was involved in the cadherin, heterotrimeric G-protein and Wnt signaling pathways. Distinct subsets of cadherins and protocadherins exhibited a sustained increase or decrease in expression. Sustained down-regulation of several heterotrimeric G-protein β- and γ-subunits was observed. In addition to altered expression of receptors for small molecule neurotransmitters, neuropeptides and endocannabinoids, changes in the expression of plasma membrane transporters and vesicular neurotransmitter transporters were also observed. The effects of chronic Cocaine and Withdrawal on the expression of genes essential to cholinergic, glutamatergic, GABAergic, peptidergic and endocannabinoid signaling are as profound as their effects on dopaminergic transmission. Simultaneous targeting of multiple Withdrawal-specific changes in gene expression may facilitate development of new therapeutic approaches that are better able to prevent relapse.
Overall design High-throughput sequence analysis of RNA prepared from the nucleus accumbens of adult male mice receiving daily injections of Saline or Cocaine, or Cocaine followed by a period of Withdrawal. Nucleus accumbens libraries were sequenced in nine lanes (three technical replicates per sample) on an Illumina GAIIx using a 37-cycle paired-end sequencing protocol. Replicates were analyzed for intra-sample disparity and read data from all three lanes were then merged into one composite data file per sample; intra-sample coefficient of determination, R2 ≥ 0.98. The composite file was used for subsequent analyses.
Contributor(s) Eipper-Mains JE, Kiraly DD, Duff MO, Horowitz MJ, McManus CJ, Eipper BA, Graveley BR, Mains RE
Citation(s) 23094851
Submission date Jan 10, 2013
Last update date May 15, 2019
Contact name Jodi Eipper-Mains
Organization name University of Connecticut Health Center
Department Genetics & Developmental Biology
Lab Graveley
Street address 263 Farmington Ave.
City Farmington
State/province CT
ZIP/Postal code 06030
Country USA
Platforms (1)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
Samples (9)
GSM1062208 NAc_saline_rep1
GSM1062209 NAc_cocaine_rep1
GSM1062210 NAc_withdrawal_rep1
BioProject PRJNA186012
SRA SRP017874

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE43410_NAc_cocaine_all.rpkm.txt.gz 732.9 Kb (ftp)(http) TXT
GSE43410_NAc_sal_coc_wit.rpkm.txt.gz 1.9 Mb (ftp)(http) TXT
GSE43410_NAc_saline_all.rpkm.txt.gz 737.3 Kb (ftp)(http) TXT
GSE43410_NAc_withdrawal_all.rpkm.txt.gz 721.8 Kb (ftp)(http) TXT
GSE43410_RAW.tar 2.1 Mb (http)(custom) TAR (of TXT)
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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