Rattus norvegicus
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PROVIDER: PRJNA167457 | ENA |
REPOSITORIES: ENA
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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.
2012-06-01 | GSE38223 | 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. 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.
2012-05-31 | E-GEOD-38223 | biostudies-arrayexpress
Project description:Methamphetamine is a widely abused, highly addictive drug. Regulation of synaptic proteins within the brain’s reward pathway modulates addiction behaviours, the progression of drug addiction and long-term changes in brain structure and function that result from drug use. Therefore, using large scale proteomics studies we aim to identify global protein expression changes within the dorsal striatum, a key brain region involved in the modulation of addiction. We performed LC-MS/MS analyses on rat striatal synaptosomes following 30 days of methamphetamine self-administration (2 hours/day) and 14 days abstinence. We identified a total of 84 differentially-expressed proteins with known roles in neuroprotection, neuroplasticity, cell cytoskeleton, energy regulation and synaptic vesicles. We identify significant expression changes in stress-induced phosphoprotein and protein Tppp, which have not previously been associated with addiction. In addition, we confirm the role of amphiphysin and phosphatidylethanolamine binding protein in addiction. This approach has provided new insight into the effects of methamphetamine self-administration on synaptic protein expression in a key brain region associated with addiction, showing a large set of differentially-expressed proteins that persist into abstinence.
2015-05-06 | PXD001443 | Pride
Project description:Methamphetamine addiction is mimicked in rats that self-administer the drug and accelerate their intake when given long access to it. Self-administration (SA) models do not include adverse consequences that are necessary to reach a diagnosis of addiction in humans. Here, we studied transcriptional consequences of methamphetamine SA and repeated foot-shocks in rat brain.
2017-09-26 | GSE95570 | GEO
Project description:Methamphetamine addiction is mimicked in rats that self-administer the drug and accelerate their intake when given long access to it. Self-administration (SA) models do not include adverse consequences that are necessary to reach a diagnosis of addiction in humans. Here, we studied transcriptional consequences of methamphetamine SA and repeated foot-shocks in rat brain.
2017-09-26 | GSE95569 | GEO
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:Striatum from rats treated with methamphetamine
| PRJNA90367 | ENA
Project description:Drug-induced alterations in transcriptional regulation play a central role in establishing the persistent neuroplasticities that occur during drug addiction. Additionally, changes in gene expression associated with drug administration provide valuable insight into the molecular basis of drug abuse. The molecular mechanisms that underlie susceptibility to psychostimulant addiction remain unknown. Identifying the common gene transcriptional responses to psychostimulants can provide a mechanistic insight to elucidate the molecular nature of drug dependence. Male Wistar rats (4 weeks old) were acclimatized for a week to their housing conditions prior to experiments. Thereafter, they were divided into two groups: (cohort 1) 4 groups of rats (n=12 rats per group) given saline only (i.p., "drug-naive" rats); and (cohort 2): 3 groups of rats given either methamphetamine, amphetamine or methylphenidate (5 mg/kg,i.p., M-CM-"M-bM-^BM-,M-EM-^Sdrug-pretreated") for 7 days (2x daily) prior to behavioral assays. Conditioned place preference (CPP) tests were conducted a day after the final drug administration. Rats which showed CPP were evaluated for self-administration of the psychostimulants. [Cohort 1] A day after the final self-administration test, brains of 2-3 rats from each subgroups (i.e. those which showed the most robust self-administration), as well as 5 rats from the control group were removed for microarray analysis. The striatum (rostral part of the caudate putamen and the nucleus accumbens [NAc]) and the prefrontal cortex were dissected and immediately frozen at -70M-CM-^BM-BM-0C. Total RNA was isolated and gene expression profiling was conducted on independent pools of total RNA from 2-5 animals per group. [Cohort 2] A day after the final self-administration test, brains of 3 rats from each subgroups (i.e. those which showed the most robust self-administration), as well as 3 rats from the control group were removed for microarray analysis. The striatum (rostral part of the caudate putamen and the nucleus accumbens [NAc]) and the prefrontal cortex were dissected and immediately frozen at -70M-BM-0C. Total RNA was isolated and gene expression profiling was conducted on independent pools of total RNA from three animals per group.
2013-06-27 | E-GEOD-43748 | biostudies-arrayexpress
Project description:Rat medial prefrontal cortex gene expression following heroin self-administration, abstinence, and extinction
| PRJNA109633 | ENA