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The effects of 24-hour withdrawal from cocaine on nucleus accumbens transcript expression.

ABSTRACT: The goal of the study was to determine how 24-hour withdrawal from cocaine affects the expression profile of transcripts in the nucleus accumbens using genome-wide RNA-sequencing. 11-week old male C57/BL6 mice were injected mice intraperitoneally (IP) with saline (0.9%) or cocaine (20 mg/kg dissolved in 0.9% saline) for 7-days consecutive days, and 24-hours after the last injection, NAc tissue was dissected. Mice were housed in group of 5 mice per cage, and all mice in a cage were injected with either saline or cocaine and thus there was no counter-balancing between groups.

ORGANISM(S): Mus musculus

PROVIDER: GSE76868 | GEO | 2016/01/27

SECONDARY ACCESSION(S): PRJNA308831

REPOSITORIES: GEO

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Project description: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. 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.

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The effects of 24-hour withdrawal from cocaine on nucleus accumbens transcript expression.

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