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Characterization of molecular signature in mice that experienced an hostile social environment during cocaine abstinence

ABSTRACT: Childhood maltreatment is associated with increased severity of substance use disorder and frequency of relapse to drug use following abstinence. However, the molecular and neurobiological substrates engaged during early traumatic events and mediating the relapse risk are poorly understood. Here, we show that the exposure to an adverse/hostile social experience in juvenile mice (social stressed mice, SS) influences the propensity to reinstate cocaine seeking after withdrawal periods. This effect is associated with an increased blood coagulation and a pauperization of brain vasculature. Moreover, a treatment with an anticoagulant agent during withdrawal abolishes the susceptibility to reinstate cocaine seeking in SS mice. These findings for the first time propose a molecular mechanism contributing to the increased susceptibility to relapse into cocaine abuse observed in individuals who had experienced childhood maltreatment. To analyze global gene expression differences between mice experiencing an hostile/adverse social environment during the third postnatal week and juvenile social isolated (SI) mice during cocaine abstinence. Peripheral Blood Mononuclear Cells were measured with Agilent mouse gene expression microarray during cocaine abstince after undergoing cocaine-seeking behavior studies by conditioned place preference test, extinction and withdrawal. Blood was collected 24 hours after the extinction test and genome-wide

ORGANISM(S): Mus musculus

PROVIDER: GSE69019 | GEO | 2015/11/15

SECONDARY ACCESSION(S): PRJNA284296

REPOSITORIES: GEO

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Rat DNA methylation in the Nucleus Accumbens in Incubation of Cocaine Craving and treatments with DNA methylation modifying drugs

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

Rat gene expression in the Nucleus Accumbens in Incubation of Cocaine Craving

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2015-02-27 | E-GEOD-66349 | biostudies-arrayexpress

Rat DNA methylation in the Nucleus Accumbens in Incubation of Cocaine Craving

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

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2021-01-28 | PXD019485 | Pride

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2020-05-19 | GSE124055 | GEO

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2010-03-16 | GSE20885 | GEO

Environmental enrichment during abstinence from cocaine self-administration opposes gene network expression changes associated with the incubation effect

Project description:Environmental enrichment (EE) is a robust intervention for reducing cocaine-seeking behaviors in animals when given during abstinence. However, the mechanisms that underlie these effects have not been well-established. We investigated the adult male rat transcriptome using RNA-sequencing (RNA-seq) following differential housing during abstinence from cocaine self-administration for either 1 or 21 days. Rats housed for 21 days of abstinence in EE displayed a significant reduction in cocaine-seeking behavior compared to rats housed in isolation. RNA-seq of the nucleus accumbens shell revealed hundreds of differentially regulated transcripts between rats of different abstinence length and housing environment, as well as within specific contrasts such as enrichment (isolated 21 days vs. enriched 21 days) or incubation (isolated 1 day vs. isolated 21 days). Ingenuity Pathway Analysis affirmed several pathways as differentially enriched based on housing condition and abstinence length including RELN, the Eif2 signaling pathway, synaptogenesis and neurogenesis pathways. Additionally, multiple pathways reversed their directionality between enrichment and incubation contrasts, potentially indicating oppositional roles across housing and abstinence length. Together, these findings reveal novel mechanisms potentially involved in the protective effects of EE against cocaine seeking, which may inform efforts to develop new pharmacological and gene therapies for treating cocaine use disorders.

2020-07-15 | GSE144606 | GEO

Abstinence from Escalation of Cocaine Intake Changes the microRNA Landscape in the Cortico-Accumbal Pathway

Project description:Cocaine administration alters the microRNA (miRNA) landscape in the cortico-accumbal pathway. These changes in miRNA can play a major role in the posttranscriptional regulation of gene expression during withdrawal. This study aimed to investigate the changes in microRNA expression in the cortico-accumbal pathway during acute withdrawal and protracted abstinence following escalated cocaine intake. Small RNA sequencing (sRNA-seq) was used to profile miRNA transcriptomic changes in the cortico-accumbal pathway [infralimbic- and prelimbic-prefrontal cortex (IL and PL) and nucleus accumbens (NAc)] of rats with extended access to cocaine self-administration followed by an 18-h withdrawal or a 4-week abstinence. An 18-h withdrawal led to differential expression (fold-change > 1.5 and p < 0.05) of 21 miRNAs in the IL, 18 miRNAs in the PL, and two miRNAs in the NAc. The mRNAs potentially targeted by these miRNAs were enriched in the following pathways: gap junctions, neurotrophin signaling, MAPK signaling, and cocaine addiction. Moreover, a 4-week abstinence led to differential expression (fold-change > 1.5 and p < 0.05) of 23 miRNAs in the IL, seven in the PL, and five miRNAs in the NAc. The mRNAs potentially targeted by these miRNAs were enriched in pathways including gap junctions, cocaine addiction, MAPK signaling, glutamatergic synapse, morphine addiction, and amphetamine addiction. Additionally, the expression levels of several miRNAs differentially expressed in either the IL or the NAc were significantly correlated with addiction behaviors. Our findings highlight the impact of acute and protracted abstinence from escalated cocaine intake on miRNA expression in the cortico-accumbal pathway, a key circuit in addiction, and suggest developing novel biomarkers and therapeutic approaches to prevent relapse by targeting abstinence-associated miRNAs and their regulated mRNAs.

2023-08-30 | GSE212651 | GEO

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2022-02-20 | GSE169628 | GEO

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2022-12-09 | GSE196374 | GEO

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