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GS87306 • Table S1: 109 genes are differentially down- (-) or up-(+ ) regulated in the CPu in D1 receptor mutant mice compared to wild-type mice after repeated cocaine administration (Whole Table) [DRG]
Chronic cocaine - D1 receptor mutant vs. Wildtype DNA microarray Gene expression differences between mutant and wildtype D1 receptor mutant and wild-type mice were injected twice daily at 11:00 and 16:00 for 7 days with 20 mg / kg of cocaine. Gene expression differences 24 h after cocaine withdrawal. p<0.05 was considered as significant. Based on this criterion, we used a cutoff of at least a 1.2-fold difference in expression for further studies. (NIF Method ID 68)
Zhang D, Zhang L, Tang Y, Zhang Q, Lou D, Sharp FR, Zhang J, Xu M
Repeated cocaine administration induces gene expression changes through the dopamine D1 receptors.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Vol 30, pp. 1443-54
Drug addiction involves compulsive drug-seeking and drug-taking despite known adverse consequences. The enduring nature of drug addiction suggests that repeated exposure to abused drugs leads to stable alterations that likely involve changes in gene expression in the brain. The dopamine D1 receptor has been shown to mediate the long-term behavioral effects of cocaine. To examine how the persistent behavioral effects of cocaine correlate with underlying changes in gene expression, we have used D1 receptor mutant and wild-type mice to identify chronic cocaine-induced gene expression changes mediated via the D1 receptors. We focused on the caudoputamen and nucleus accumbens, two key brain regions that mediate the long-term effects of cocaine. Our analyses demonstrate that repeated cocaine administration induces changes in the expression of 109 genes, including those encoding the stromal cell-derived factor I, insulin-like growth factor binding protein 6, sigma 1 receptor, regulators of G-protein signaling protein 4, Wnt1 responsive Cdc42 homolog, Ca2+/calmodulin-dependent protein kinase II alpha subunit, and cyclin D2, via the D1 receptors. Moreover, the seven genes contain AP-1 binding sites in their promoter regions. These results suggest that genes encoding certain extracellular factors, membrane receptors and modulators, and intracellular signaling molecules, among others, are regulated by cocaine via the D1 receptor, and these AP-1 transcription complex-regulated genes might contribute to persistent cocaine-induced behavioral changes.
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