Cocaine self-administration alters brain NADH dehydrogenase mRNA levels

Couceyro, Pastor R.; Shoaib, Mohammed; McCoy, Michael T.; Goldberg, Steven R.; Kuhar, Michael J.

doi:10.1097/00001756-199707280-00006

Cited by 9 publications

(8 citation statements)

References 10 publications

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“…An important finding was that these 25 transcripts encode for a wide variety of proteins involved in neuronal growth, apoptosis, neurotransmission, transcription, translation and cell metabolism. This is consistent with reports from others, showing that addictive drugs are able to induce (long-lasting) alterations in neuronal morphology (Robinson and Kolb, 1999a,b;Robinson et al, 2001), neurotransmission (Vanderschuren and , transcription (Cha et al, 1997;Kelz and Nestler, 2000;Mackler et al, 2000) and cell metabolism (Couceyro et al, 1997) in the NAc. Also, drug-induced apoptosis-related processes have been shown in the brain (Boronat et al, 2001;Hu et al, 2002).…”

Section: Identification Of Transcripts In the Librarysupporting

confidence: 93%

Long-Term Gene Expression in the Nucleus Accumbens Following Heroin Administration is Subregion-Specific and Depends on the Nature of Drug Administration

et al. 2005

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Repeated exposure to addictive drugs results in long-lasting neuroadaptations in the brain, especially in the mesocorticolimbic system. Within this system, the nucleus accumbens (NAc) plays a major integrative role. As such, the NAc has been shown to be a target of short- and long-lasting drug-induced neuroadaptations at the levels of neurotransmission and cellular morphology. The long-lasting neuroadaptations might depend critically on alterations in gene expression. Recently, we obtained a set of transcripts by means of subtractive hybridization, of which the expression was decreased in the rat NAc shell after long-term extinction of intravenous heroin self-administration. Interestingly, the majority of these transcripts were also down-regulated upon long-term extinction of cocaine self-administration. Using the yoked-control operant paradigm, it was shown that non-contingent administration of these drugs resulted in a totally different gene expression profile. However, in the rat NAc core, both self-administration and non-contingent heroin administration induced a qualitatively similar expression profile. Hence, cognitive processes associated with drug self-administration seem to direct the long-term genomic responses in the NAc shell, whereas the NAc core might primarily mediate the persistent pharmacological effects of addictive drugs (including Pavlovian conditioning).

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Section: Identification Of Transcripts In the Librarysupporting

confidence: 93%

Long-Term Gene Expression in the Nucleus Accumbens Following Heroin Administration is Subregion-Specific and Depends on the Nature of Drug Administration

et al. 2005

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“…It was previously reported that cocaine self-administration resulted in the reduced expression (by 26%) of NADH subunit 6 gene expression in the nucleus accumbens. 8 Our results further support the involvement of the mitochondrial genome in the mechanism(s) of action of cocaine.…”

Section: Discussionsupporting

confidence: 75%

Cocaine Downregulates the Expression of the Mitochondrial Genome in Rat Brain

Diétrich

Poirier

Aunis

et al. 2004

Annals of the New York Academy of Sciences

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Analysis by differential display of genes induced in response to acute cocaine administration to rats revealed the significant downregulation of several mitochondrial genes in the cingulate cortex, including the subunits 1, 2, 4, 5, and 6 of NADH dehydrogenase and the subunit 2 of cytochrome c oxidase. Although the mechanism of the downregulation of expression of these mitochondrial genes by cocaine is presently not well understood, one can envisage that it involves an increased production of reactive oxygen species in cells of the cerebral cortex.

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“…Six of 10 downregulated genes shown in Table IVB are associated with energy metabolism in mitochondria. Region-specific regulation of mitochondrial ␤-nicotinamide-adenine dinucleotide (NADH) dehydrogenase by cocaine was demonstrated in a rat cocaine self-administration model (Couceyro et al, 1997). In that report, downregulation of NADH dehydrogenase subunit 6 in the nucleus accumbens, upregulation in the hypothalamus, and no change in the CPu were observed immediately after the last cocaine self-administration session.…”

Section: Cocaine-responsive Gene Expressionmentioning

confidence: 91%

Differential gene expression in the rat caudate putamen after “binge” cocaine administration: Advantage of triplicate microarray analysis

Yuferov

Kroslak

LaForge

et al. 2003

Synapse

139

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Rat genome U34A (Affymetrix) oligonucleotide microarrays were used to analyze changes in gene expression in the caudate putamen (CPu) of Fischer rats induced by 1 and 3 days of "binge" cocaine (or saline) administration. A triplicate array assay of pooled RNA of each treatment group was used to evaluate the technical variability and sensitivity of microarrays. Cocaine-regulated genes were identified using the Affymetrix MAS 5.0 and Data Mining Tool v. 3. Eighty-nine upregulated and eight downregulated genes/ESTs were found after 1 day of "binge" cocaine. Following 3 days of cocaine treatment we identified 21 upregulated and 17 downregulated genes/ESTs. RNase protection assays of selected genes confirmed reliability of changes identified by the microarrays at the level of > or =1.40-fold increase. Many genes upregulated in the CPu by cocaine were immediate early genes for transcription factors and for "effector" proteins (e.g., vesl/Homer1a, Arc, synaptotagmin IV). Acute "binge" cocaine also increased mRNA levels for glutamate receptor GluR2, dopamine receptor D1, and a number of phosphatases. Genes downregulated by cocaine include several genes associated with energy metabolism in mitochondria, as well as the phosphatydylinositol-4 kinase and the regulator of G-protein signaling protein 4 (RGS4). A differential expression of somatostatin receptor SSTR2, not known to be a cocaine-responsive gene, as well as the clock gene Per2, were found by microarrays and confirmed by RNase protection assay. These results demonstrate the potential of microarrays in profiling gene expression with > or =40% increase or > or =14% decrease in mRNA levels for discovery of novel cocaine-responsive genes.

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Cocaine self-administration alters brain NADH dehydrogenase mRNA levels

Cited by 9 publications

References 10 publications

Long-Term Gene Expression in the Nucleus Accumbens Following Heroin Administration is Subregion-Specific and Depends on the Nature of Drug Administration

Long-Term Gene Expression in the Nucleus Accumbens Following Heroin Administration is Subregion-Specific and Depends on the Nature of Drug Administration

Cocaine Downregulates the Expression of the Mitochondrial Genome in Rat Brain

Differential gene expression in the rat caudate putamen after “binge” cocaine administration: Advantage of triplicate microarray analysis

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