Transcriptional signatures of heroin intake and relapse throughout the brain reward circuitry in male mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA947905 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23948700_1.fastq.gz | Fastqsanger.gz | |||
| SRR23948700_2.fastq.gz | Fastqsanger.gz | |||
| SRR23948800_1.fastq.gz | Fastqsanger.gz | |||
| SRR23948800_2.fastq.gz | Fastqsanger.gz | |||
| SRR23948900_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 610 |
Similar Datasets
Project description:Identifying changes in gene expression throughout the brain reward system induced across various conditions of heroin self-administration in mice as a model of opioid use disorder
2023-04-25 | GSE228031 | 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: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:The nucleus accumbens plays a central role in ther regulation of reward, emotion, motivation and goal-directed behavior. Gene expression impairments in this brain region are of crucial interest to understand the neurobiological underpinnings of heroin use disorder. We used the Affymetrix HG-U133A microarray to assess gene expression in the post-mortem nucleus accumbens of human heroin users and control subjects and identified differentially expressed genes.
2016-10-12 | GSE87823 | 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:The putamen plays a central role in ther regulation of reward, emotion, motivation and goal-directed behavior. Genome accessibility changes in this brain region are of crucial interest to understand the neurobiological underpinnings of heroin use disorder.
2020-07-01 | GSE136042 | GEO
Project description:Cocaine self-administration alters transcriptome-wide responses in the brain's reward circuitry
| PRJNA433508 | ENA
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:Global changes in gene expression that underlie the circuit and behavioral dysregulation associated with cocaine addiction remain incompletely understood. Here, we determined how a history of cocaine self-administration (SA) “re-programs” transcriptome-wide responses at baseline and in response to cocaine re-exposure after prolonged withdrawal (WD). We assigned male mice to one of six groups: saline or cocaine SA + 24 hr WD; or saline/cocaine SA + 30 d WD + an acute saline/cocaine challenge within the previous drug-paired context. RNA-seq was then conducted on six interconnected brain reward regions. We focused on patterns of gene expression that were altered by cocaine SA, in particular, molecular targets that show priming or desensitization upon re-exposure to cocaine. Genes that were affected uniquely by acute cocaine after cocaine SA+WD displayed region-specific regulation. The greatest number of regulated genes were seen in nucleus accumbens, dorsal striatum, and basolateral amygdala. Further analysis revealed several transcription factors as key upstream regulators in these three regions, including several not previously implicated in cocaine action. Regulation of subsets of these primed and desensitized genes correlated robustly with SA behavior displayed by individual mice. For example, analysis of transcriptome-wide expression changes revealed that genes associated with cocaine intake respond to contextual information in a region-specific manner. This comprehensive picture of transcriptome-wide regulation by cocaine SA and WD throughout the brain’s reward circuitry provides new insight into the molecular basis of cocaine addiction, which will guide future studies of the key molecular pathways involved.
2018-08-22 | GSE110344 | GEO
Project description:Noncoding RNAs, especially microRNAs (miRNAs) have been implicated in the regulation of neuronal functions, such as learning, cognition and memory formation. However, the particular miRNAs involved in drug-induced behavioral plasticity are largely unknown. Here we report a novel regulator, miR-218, that inhibits heroin-induced behavioral plasticity. Network propagation-based method revealed several miRNAs that play key roles in drug-addiction, among which, miR-218 was decreased in nucleus accumbens (NAc) after chronic exposure to heroin. Lentiviral overexpression of miR-218 in NAc could inhibit heroin-induced reinforcement in both conditioning place preference (CPP) test and heroin self-administration (SA) experiment. Luciferase activity assay indicated miR-218 could regulate neuroplasticity related genes and directly target Mecp2 3’UTR. Consistently, Mecp2-/y mice exhibited reduced heroin seeking behavior in CPP test. These data reveal a functional role of miR-218 and its target, Mecp2, in the regulation of heroin-induced behavioral plasticity.
2017-03-08 | GSE89202 | GEO