Transcriptional effects of chronic heroin and methamphetamine treatment in the mouse striatum
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE30305 | GEO | 2012/06/21
SECONDARY ACCESSION(S): PRJNA143581
REPOSITORIES: GEO
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Project description:To identify molecular effects of chronic drug treatment, heroin and methamphetamine treated animals were compared with saline treated animals at multiple time-points using microarray technology. Gene expression profile was assessed 14 h after the last dose of 1, 3, 6 or 12 days drug treatment and after 13, 15, 18 or 24 days of withdrawal. Animals were injected intraperitoneally with saline (SAL) (Polfa, Lublin, Poland), heroin (synthesized from morphine in Institute of Pharmacology PAS, Krakow, Poland) or D-methamphetamine (Sigma-Aldrich, Poznan, Poland) twice a day for consecutive 12 days in increasing doses. The Methamphetamine last dose (8 mg/kg) was four times greater than the first dose (2 mg/kg). It was also the case for heroin (40 and 10 mg/kg respectively). Mice were sacrificed by decapitation after 1, 3, 6 or 12 days of treatment or after 13, 15, 18 or 24 days of withdrawal.
2012-06-20 | E-GEOD-30305 | biostudies-arrayexpress
Project description:In summary, we characterized genomic signatures of response to drugs of abuse and we found positive correlations between the drug-induced expression and various behavioral effects. These signatures are formed by two dynamically inducible transcriptional networks: (1) CREB/SRF-dependent gene pattern that appears to be related to drug-induced neuronal activity, (2) the pattern of genes controlled at least in part via release of glucocorticoids and androgens that are associated with rewarding and harmful drug effects. The discovery of co-expressed networks of genes allowed for the identification of master-switch controlling factors involved in molecular response to the drugs. Finally, using the pharmacological tools we were able to dissect and inhibit particular gene expression patterns from genomic profile. Type: Drug response, Time-course, Gene expression profiling with Illumina Microarrays Keywords: Addiction, Drugs of abuse, Time-course, Immediate Early Genes, Glucocorticoid receptor dependent genes, Cocaine, Heroin, Nicotine, Ethanol, Morphine, Methamphetamine The microarray experiment was performed to analyze time-course of drug-induced transcriptional response in C57BL/6J mouse striatum. Six the most addictive and harming drugs of abuse (morphine 20 mg/kg, heroin 10 mg/kg, ethanol 2 g/kg, nicotine 1 mg/kg, methamphetamine 2 mg/kg or cocaine 25 mg/kg, i.p.) were selected for the comparison. Drug doses were previously reported as rewarding in mice and further tested in our laboratory. To analyze dynamics of early, intermediate and relatively late changes of mRNA abundance the experiment was performed in four time points (1, 2, 4 and 8h after drug administration). To exclude influence of drug injection and circadian rhythm on gene expression profile, control groups of saline treated and naïve animals were prepared for each time point. Design of the experiment assumed pooling of two animals per each array and using of three independent arrays per group. To provide appropriate balance in the whole dataset groups were equally divided between the array hybridization batches. 'Complete' normalized data and non-normalized data (containing control rows not represented in Platform GPL6105) are linked below as supplementary files.
2010-04-14 | E-GEOD-15774 | biostudies-arrayexpress
Project description:Comparison of striatum from rats treated with either saline or 40mg/kg methamphetamine Keywords: other
2004-09-30 | GSE1711 | GEO
Project description:Comparison of striatum from rats treated with either saline or 40mg/kg methamphetamine Keywords: other
2004-09-30 | E-GEOD-1711 | biostudies-arrayexpress
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: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:Methamphetamine abuse continues to be a worldwide problem, damaging the individual user as well as society. Only minimal information exists on molecular changes in the brain that result from methamphetamine administered in patterns typical of human abusers. In order to investigate such changes, we examined the effect of methamphetamine on the transcriptional profile in brains of monkeys. Gene expression profiling of the caudate and hippocampus identified protein disulfide isomerase family member A3 (PDIA3) to be significantly up-regulated in the animals treated with methamphetamine as compared to saline treated control monkeys. Treatment of primary rat neurons with methamphetamine revealed an up-regulation of PDIA3, showing a direct effect of methamphetamine on neurons to increase PDIA3. In vitro studies using a neuroblastoma cell line demonstrated that PDIA3 expression protects against methamphetamine-induced cell toxicity and methamphetamine-induced intracellular reactive oxygen species production, revealing a neuroprotective role for PDIA3. The current study implicates PDIA3 to be an important cellular neuroprotective mechanism against a toxic drug, and as a potential target for therapeutic investigations. To study the effects of chronic METH effects on the brain
2011-11-15 | E-GEOD-33707 | biostudies-arrayexpress
Project description:Methamphetamine abuse continues to be a worldwide problem, damaging the individual user as well as society. Only minimal information exists on molecular changes in the brain that result from methamphetamine administered in patterns typical of human abusers. In order to investigate such changes, we examined the effect of methamphetamine on the transcriptional profile in brains of monkeys. Gene expression profiling of the caudate and hippocampus identified protein disulfide isomerase family member A3 (PDIA3) to be significantly up-regulated in the animals treated with methamphetamine as compared to saline treated control monkeys. Treatment of primary rat neurons with methamphetamine revealed an up-regulation of PDIA3, showing a direct effect of methamphetamine on neurons to increase PDIA3. In vitro studies using a neuroblastoma cell line demonstrated that PDIA3 expression protects against methamphetamine-induced cell toxicity and methamphetamine-induced intracellular reactive oxygen species production, revealing a neuroprotective role for PDIA3. The current study implicates PDIA3 to be an important cellular neuroprotective mechanism against a toxic drug, and as a potential target for therapeutic investigations.
2011-11-15 | GSE33707 | GEO
Project description:Our goal was to examine whether the HIV Tat peptide, which is usually secreted from infected cells and has the potential to act in other cell types, alters gene expression in the Central Nervous System, and whether a drug abuse co-morbidity, in the case Methamphetamine, can play a role in further modifying gene expression. In order to address the effects of HIV Tat and Methamphetamine, alone and combined, we used an in vivo mouse model that has been described to mimic several aspects of neuroHIV, including changes in inflammatory markers, and decreased expression of dopamine receptors. These animals are transgenic mice, which upon treatment with with doxycycline for 10 days, express TAT protein under the control of the glial fibrilary associated protein (GFAP) promoter in the brain. They were treated with Meth and Saline for identification of gene expression changes that result from Tat or Methamphetamine alone, or from their interaction. There was an overall suppression of gene expression by Methamphetamine, in Tat- mice. The expression of Tat caused most Meth-induced changes to remain at control levels.
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Project description:Methamphetamine can trigger dopamine releasing in human brain, now used as abuse drug. Some studies have shown that specific genes and proteins responded to, methamphetamine, but little is known about the overall “omic” response of organisms to this illicit substance. Here we demonstrate that Drosophila melanogaster has the potential to give us significant insights into evolutionarily conserved responses to methamphetamine. We performed metabolome, proteome, and transciptome profiling with Drosophila treated with methamphetamine. The proteomic profiling revealed responses associated with known physiological problems that occur with methamphetamine usage in mammals. The metabolomic result showed that the metabolite trehalose was decreased significantly after methamphetamine exposure, suggesting an oxidative stress response to this drug. Many of the differential transcribed genes, including detoxification enzymes, had the potential transcription factor-binding motif YY1 associated with their upstream regulatory regions. YY1 is known to be responsive to amphetamines in mammals.
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