Ontology highlight
ABSTRACT:
PROVIDER: PRJNA855269 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19963700.fastq.gz | Fastqsanger.gz | |||
| SRR19963701.fastq.gz | Fastqsanger.gz | |||
| SRR19963702.fastq.gz | Fastqsanger.gz | |||
| SRR19963703.fastq.gz | Fastqsanger.gz | |||
| SRR19963704.fastq.gz | Fastqsanger.gz |
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Project description:This study aimed to identify changes in novel miRNAs and their target genes during METH self-administration and investigate their roles in METH-induced locomotion. RNA sequencing analysis revealed that mir-183-5p was upregulated in the striatum of METH self-administered rats, and target gene prediction revealed that the glucocorticoid receptor (GR) gene, Nr3c1, was a potential target gene for mir-183-5p. We confirmed that single and repeated METH administrations increased METH-induced locomotion and plasma corticosterone levels in rats.
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Project description:This study aimed to identify changes in novel miRNAs and their target genes during METH self-administration and investigate their roles in METH-induced locomotion. RNA sequencing analysis revealed that mir-183-5p was upregulated in the striatum of METH self-administered rats, and target gene prediction revealed that the glucocorticoid receptor (GR) gene, Nr3c1, was a potential target gene for mir-183-5p. We confirmed that single and repeated METH administrations increased METH-induced locomotion and plasma corticosterone levels in rats.
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Project description:Transcriptional profiling of striatum in METH self-administered rats
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Project description:Transcriptional profiling of striatum in METH self-administered rats [mRNA]
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Project description:Methamphetamine (METH) use disorder (MUD) is a neuropsychiatric disorder with loss of self-control over drug intake despite of negative consequences. The behavioral consequences of long-term METH intake on compulsive and non-compulsive individuals remain unclear. Herein we trained rats to self-administered METH 1st for 22 days than 8 days of foot-shock and 15 days of abstinence. Which was followed by 12 days of reinstatement to METH self-administration then 3 days of foot-shock and 15 days of abstinence. After 1st foot-shock phase we found two phenotypes based on their METH intake i.e., shock resistance (SR, compulsive), and shock sensitive (SS, non-compulsive). Interestingly during reinstatement of METH self-administration then foot-shock, some (resurgent shock resistance, RSR) non-compulsive rats, displayed compulsive METH intake behavior. During both abstinence period rats were tested for drug seeking behavior and SR rats displayed higher METH seeking then RSR and SS. 24 hour after 2nd withdrawal day testing, we compared transcriptional and epigenetic changes in dorsal striatum.
2024-09-25 | GSE220896 | GEO
Project description:Neuroplastic changes in the dorsal striatum participate in the transition from casual drug use to habitual and compulsive drug taking. These alterations might also play a critical role in the development of methamphetamine (METH) addiction. Nevertheless, the molecular substrates that underlie habitual METH consumption have yet to be elucidated. Therefore, in the present study, we examined the influence of METH self-administration on the expression of genes and proteins of interest, as potential substrates of METH-induced neuronal plasticity in the dorsal striatum. Rats self-administered METH (0.1 mg/kg/injection, i.v.) during 15 h sessions for 8 d and were euthanized after 2 h, 24 h, or 1 month of abstinence. Compared to yoked saline control, METH self-administration induced increases in the mRNA expression of the transcription factors, c-fos and fosb, the neurotrophic factor, Bdnf, and of the synaptic protein, synaptophysin (Syp) at 2 h after cessation of drug exposure. METH self-administration also caused changes in FosB, BDNF and TrkB protein levels, with increases at 2 and 24 h but decreases observed after 1 month of drug abstinence. Importantly, METH exposure caused increases in the levels of H3K4me3 and pCREB after 2 and 24 h of abstinence. Chromatin immunoprecipitation followed by qPCR was used to clarify the role of these proteins in the regulation of gene expression. We found that METH self-administration caused enrichment of pCREB, but not of H3K4me3, on the promoters of c-fos, fosb, Bdnf and Syp at 2 h after drug cessation. These data indicate that METH-induced activation of their transcription is mediated, in part, by pCREB-dependent epigenetic phenomena. Thus, METH self-administration might trigger epigenetic changes that caused alterations in the expression of genes and proteins serving as substrates for addiction-related synaptic plasticity.
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Project description:Methamphetamine (METH) is a powerful stimulant that has caused addiction (compulsive drug seeking and taking behavior) in millions of people world-wide. METH abuse is also associated with negative impact on the brain. One feature of addiction is uncontrollable drug seeking despite adverse consequences and becomes habitual. To mimic this in a rat model, rats with a history of METH use are given the opportunity to earn METH accompanied by aversive shocks on their feet. Rats that continue to take METH are shock-resistant (SR) and rats that reduce their METH intake are shock-sensitive (SS ).Rats that self-administered saline are controls (CT). In addition, we used controls for shock paradigm. For this purpose, when METH SA rat received a shock, the saline SA rat was also shocked. The separate groups of rats that were yoked (Y) to the corresponding METH shock-resistant (SR) and shock-sensitive (SS) rats are termed YSR and YSS, respectively.
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Project description:Neuroplastic changes in the dorsal striatum participate in the transition from casual drug use to habitual and compulsive drug taking. These alterations might also play a critical role in the development of methamphetamine (METH) addiction. Nevertheless, the molecular substrates that underlie habitual METH consumption have yet to be elucidated. Therefore, in the present study, we examined the influence of METH self-administration on the expression of genes and proteins of interest, as potential substrates of METH-induced neuronal plasticity in the dorsal striatum. Rats self-administered METH (0.1 mg/kg/injection, i.v.) during 15 h sessions for 8 d and were euthanized after 2 h, 24 h, or 1 month of abstinence. Compared to yoked saline control, METH self-administration induced increases in the mRNA expression of the transcription factors, c-fos and fosb, the neurotrophic factor, Bdnf, and of the synaptic protein, synaptophysin (Syp) at 2 h after cessation of drug exposure. METH self-administration also caused changes in FosB, BDNF and TrkB protein levels, with increases at 2 and 24 h but decreases observed after 1 month of drug abstinence. Importantly, METH exposure caused increases in the levels of H3K4me3 and pCREB after 2 and 24 h of abstinence. Chromatin immunoprecipitation followed by qPCR was used to clarify the role of these proteins in the regulation of gene expression. We found that METH self-administration caused enrichment of pCREB, but not of H3K4me3, on the promoters of c-fos, fosb, Bdnf and Syp at 2 h after drug cessation. These data indicate that METH-induced activation of their transcription is mediated, in part, by pCREB-dependent epigenetic phenomena. Thus, METH self-administration might trigger epigenetic changes that caused alterations in the expression of genes and proteins serving as substrates for addiction-related synaptic plasticity. Animals were trained to self-administer METH for 8 d as described in the paper, dorsal striata were isolated 2 h, 24 h and 1 month after the final self-administration session. RNA extraction, RNA labeling and microarray hybridization were performed. In brief, total RNA was isolated from the samples using RNeasy Mini Kit (QIAGEN, Valencia, CA). RNA concentration and integrity was determined using Agilent BioAnalyzer (Agilent, Santa Clara, CA). Samples were stored at -80ºC. Microarray hybridization was done using RatRef-12 Expression BeadChips arrays (22 523 probes) (Illumina Inc., San Diego, CA). A 600 ng of total RNA from each sample was amplified using Illumina RNA Amplification kit (Ambion, Austin, TX). Single-stranded RNA (cRNA) was generated and labeled by incorporating biotin-16-UTP (Roche Diagnostics, Indianapolis, IN). 750 ng of each cRNA sample were hybridized to Illumina arrays at 55°C overnight according to the Gene Expression Protocol for BeadStation (Illumina Inc.). Hybridized cRNA was detected with cyanine3-streptavidin (GE Healthcare, Piscataway, NJ) and quantified using Illumina's BeadStation 500GX scanner.
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Project description:Transcriptional profiling of whisker follicles and of the striatum in methamphetamine self-administered rats
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