Transcriptional characterization of cocaine withdrawal versus extinction within nucleus accumbens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1101032 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Neurobiological alterations seen in addiction amplify during abstinence and compromise relapse prevention. Cocaine use disorder (CUD) exemplifies this phenomenon in which reward regions such as nucleus accumbens (NAc) undergo withdrawal-associated modifications. While genome-wide transcriptional changes in NAc are linked to specific addiction phases, these have not been examined in a context- and NAc-subregion-specific manner during withdrawal vs. extinction. We used cocaine self-administration in rats combined with RNA-sequencing of NAc core and shell to transcriptionally profile withdrawal in the home-cage, in the previous drug context, or after extinction. As expected, home-cage withdrawal maintained drug seeking, whereas extinction reduced it. Conversely, withdrawal involving the drug context increased seeking. Bioinformatic analyses revealed specific gene expression patterns and networks associated with these states. Comparing NAc datasets of CUD patients highlighted conserved transcriptomic signatures with rats experiencing withdrawal in the drug context. Together, this work reveals fundamental mechanisms that can be targeted to attenuate relapse.
2025-01-13 | GSE264129 | GEO
Project description:DNA methylation profiling of nucleus Accumbens of rats that self administered cocaine, were subjected to 30 withdrawal days, were treated with aCSF, RG108 or SAM and were subjected to extinction tests. The groups consist of: 1. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 30 days, were injected in the nucleus accumbens with aCSF and were subjected to an extinction test for assessment of cue-induced cocaine-seeking behavior (aCSF) 2. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 30 days, were injected in the nucleus accumbens with RG108 and were subjected to an extinction test for assessment of cue-induced cocaine-seeking behavior (RG108) 3. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 30 days, were injected in the nucleus accumbens with SAM and were subjected to an extinction test for assessment of cue-induced cocaine-seeking behavior (SAM)
2015-02-27 | E-GEOD-66347 | biostudies-arrayexpress
Project description:Gene expression profiling of nucleus Accumbens of rats that self administered cocaine and were subjected to 1 or 30 withdrawal days with or without extinction tests. The groups consist of 1. Saline rats (Sal.) 2. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 1 day (1W) 3. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 1 day and to an extinction test for assessment of cue-induced cocaine-seeking behavior (1C) 4. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 30 days (30W) 5. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 30 days and to an extinction test for assessment of cue-induced cocaine-seeking behavior (30C)
2015-02-27 | E-GEOD-66349 | biostudies-arrayexpress
Project description:DNA methylation profiling of nucleus Accumbens of rats that self administered cocaine and were subjected to 1 or 30 withdrawal days with or without extinction tests. The groups consist of 1. Saline rats (Sal.) 2. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 1 day (1W) 3. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 1 day and to an extinction test for assessment of cue-induced cocaine-seeking behavior (1C) 4. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 30 days (30W) 5. Rats that self-administered cocaine for 10 days and that were subjected to a withdrawal period of 30 days and to an extinction test for assessment of cue-induced cocaine-seeking behavior (30C)
2015-02-27 | E-GEOD-66348 | biostudies-arrayexpress
Project description:Gene expression profiling of nucleus Accumbens of rats that self administered cocaine and were subjected to 1 or 30 withdrawal days with or without extinction tests.
2015-02-27 | GSE66349 | GEO
Project description:DNA methylation profiling of nucleus Accumbens of rats that self administered cocaine and were subjected to 1 or 30 withdrawal days with or without extinction tests.
2015-02-27 | GSE66348 | GEO
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.
2013-01-10 | E-GEOD-43410 | biostudies-arrayexpress
Project description:DNA methylation profiling of nucleus Accumbens of rats that self administered cocaine, were subjected to 30 withdrawal days, were treated with aCSF, RG108 or SAM and were subjected to extinction tests.
2015-02-27 | GSE66347 | GEO
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.
2013-01-10 | GSE43410 | GEO
Project description:Neuroadaptations in the nucleus accumbens (NAc) underlie cue-induced cocaine craving that intensifies (“incubates”) during withdrawal and contributes to persistent relapse vulnerability. Long-lasting gene changes govern perpetual behavioral abnormalities but the role of epigenetic plasticity in cocaine craving during prolonged withdrawal is poorly understood. Here we show that chromatin remodeler INO80 in the NAc mediates cocaine-induced, withdrawal-dependent plasticity and incubated cocaine craving.
2019-10-29 | GSE119627 | GEO