Small-RNA sequencing after forced abstinence from heroin self-administration in male rats
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE205451 | GEO | 2023/04/12
REPOSITORIES: GEO
Similar Datasets
Project description:We report the miRNAs differentially expressed in the orbitofrontal cortex of adult male rats that self-administered heroin after 2 days of forced abstinence.
2024-02-28 | GSE237409 | GEO
Project description:Several studies have investigated changes induced by drug exposure, but few reports have described changes that persist following relapse. In the present study, genome-wide analysis of gene expression was conducted in rats that expressed behavioral incubation of heroin-seeking and goal-directed behavior. The medial prefrontal cortex (mPFC) is important in mediating goal-directed behavior and also was the target of this analysis. Rats were trained to self-administer heroin (0.06 mg/0.2 ml infusion) during 3 hour daily sessions for 14 days. Following the self-administration period, rats were reintroduced to the self-administration chambers for a 90-minute extinction session. The extinction session occurred either 1 day or 14 days following the final self-administration session. Behavioral data demonstrated incubation (increased expression) of heroin-seeking and goal-directed behavior after the 14 day abstinent period. Whole genome analysis was performed and selected results were confirmed by quantitative real-time PCR (RT-qPCR). Microarrays identified 66 genes whose expression was identified as changed by at least 1.4 fold (p<0.02) following 14 days of abstinence and the 90-minute extinction session, and seven of the genes on which RT-qPCR was performed were confirmed (BDNF, Calb1, Dusp5, Dusp6, EGR1, NPY, RGS2). Ontological analysis indicates that several of the genes with changed expression in this study are important for behavior and learning. The importance of drug-seeking behavior and memory of previous sessions of drug-taking suggest that such genes may be important for relapse. The global gene expression analysis adds to the knowledge of heroin-induced changes and further highlights similarities between heroin and other drugs of abuse. Keywords: heroin self-administration cRNA from 6 rats that self-administered heroin was compared to cRNA from 5 rats that received yoked infusions of saline.
2009-01-29 | E-GEOD-13166 | biostudies-arrayexpress
Project description:Several studies have investigated changes induced by drug exposure, but few reports have described changes that persist following relapse. In the present study, genome-wide analysis of gene expression was conducted in rats that expressed behavioral incubation of heroin-seeking and goal-directed behavior. The medial prefrontal cortex (mPFC) is important in mediating goal-directed behavior and also was the target of this analysis. Rats were trained to self-administer heroin (0.06 mg/0.2 ml infusion) during 3 hour daily sessions for 14 days. Following the self-administration period, rats were reintroduced to the self-administration chambers for a 90-minute extinction session. The extinction session occurred either 1 day or 14 days following the final self-administration session. Behavioral data demonstrated incubation (increased expression) of heroin-seeking and goal-directed behavior after the 14 day abstinent period. Whole genome analysis was performed and selected results were confirmed by quantitative real-time PCR (RT-qPCR). Microarrays identified 66 genes whose expression was identified as changed by at least 1.4 fold (p<0.02) following 14 days of abstinence and the 90-minute extinction session, and seven of the genes on which RT-qPCR was performed were confirmed (BDNF, Calb1, Dusp5, Dusp6, EGR1, NPY, RGS2). Ontological analysis indicates that several of the genes with changed expression in this study are important for behavior and learning. The importance of drug-seeking behavior and memory of previous sessions of drug-taking suggest that such genes may be important for relapse. The global gene expression analysis adds to the knowledge of heroin-induced changes and further highlights similarities between heroin and other drugs of abuse. Keywords: heroin self-administration
2009-01-30 | GSE13166 | GEO
Project description:In this study we identified circular RNAs that are regulated in the orbitofrontal cortex after chronic heroin self-administration of a dosage of 0.03mg/kg/infusion or sucrose self-administration.
2022-02-16 | GSE189192 | GEO
Project description:Persistent transcriptional events in ventral tegmental area (VTA) and other reward relevant brain regions contribute to enduring behavioral adaptations that characterize substance use disorder (SUD). Recent data from our laboratory indicate that aberrant accumulation of the newly discovered histone post-translational modification (PTM), H3 dopaminylation at glutamine 5 (H3Q5dop), contributes significantly to cocaine-seeking behavior following prolonged periods of abstinence. It remained unclear, however, whether this modification is important for relapse vulnerability in the context of other drugs of abuse, such as opioids. Here, we showed that H3Q5dop plays a critical role in heroin-mediated transcriptional plasticity in midbrain. In rats undergoing abstinence from heroin self-administration (SA), we found acute and persistent accumulation of H3Q5dop in VTA. By attenuating H3Q5dop during abstinence, we both altered gene expression programs associated with heroin withdrawal and reduced heroin-primed reinstatement behavior. These findings thus establish an essential role for H3Q5dop, and its downstream transcriptional consequences, in opioid-induced plasticity in VTA.
2022-02-20 | GSE169628 | GEO
Project description:Many studies of cocaine-responsive gene expression have focused on changes occurring during cocaine exposure, but few studies have examined the persistence of these changes with cocaine abstinence. Persistent changes in gene expression, as well as alterations induced during abstinence may underlie long-lasting drug craving and relapse liability. Results: Whole-genome expression analysis was conducted on a rat cocaine binge-abstinence model that has previously been demonstrated to engender increased drug seeking and taking with abstinence. Gene expression changes in two mesolimbic terminal fields (mPFC and NAc) were identified in a comparison of cocaine-naïve rats with rats after 10 days of cocaine selfadministration followed by 1, 10, or 100 days of enforced abstinence (n=6-11 per group). A total of 1,461 genes in the mPFC and 414 genes in the NAc were altered between at least two time points (ANOVA, p<0.05; ±1.4 fold-change). These genes can be subdivided into: 1) changes with cocaine self-administration that do not persist into periods of abstinence, 2) changes with cocaine self-administration that persist with abstinence, 3) and those not changed with cocaine self-administration, but changed during enforced abstinence. qPCR analysis was conducted to confirm gene expression changes observed in the microarray analysis.
2010-03-16 | GSE20885 | GEO
Project description:Opioid abuse produces enduring associations between the drug euphoria and features of the drug-taking experience, and these powerful associations can trigger relapse in individuals recovering from opioid use disorder. We show here that the epigenetic enzyme, histone deacetylase 5 (HDAC5), functions in the nucleus accumbens (NAc) during active heroin use to limit future relapse-like behavior. Moreover, enhancing HDAC5 function in NAc dramatically suppresses context-associated and reinstated heroin seeking behaviors, but it does not impact sucrose seeking. We also find that HDAC5 functions within dopamine D1 receptor-expressing medium spiny neurons (MSNs) to suppress cue-induced heroin seeking, but within dopamine D2 receptor-expressing MSNs to suppress drug-primed heroin seeking. Using cell type-specific transcriptomics analysis, we found that HDAC5 reduces expression of numerous genes linked to ion transport, and it decreases intrinsic excitability of NAc MSNs, suggesting that HDAC5 limits relapse vulnerability by suppressing NAc MSN firing rates during active heroin use. We used microarrays to define genes differentially expressed in the presence or absence of AAV2-DIO-HDAC5-3SA in both D1 and D2 cell-types derived from Nucleus accumbens following vTRAP.
2023-03-01 | GSE199985 | GEO
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
Project description:Illumina 450K Infinium microarray profiling of DNA methylation in FACS-separated neuronal nuclei from the postmortem orbitofrontal (OF) cortex of heroin users, controls and sucide individuals.
2017-05-30 | GSE98203 | GEO
Project description:circular RNA expression in the rat orbitofrontal cortex after self-administration of heroin or sucrose
| PRJNA781915 | ENA