The effects of chronic treatment with topiramate on gene expression in the rat prefrontal cortex. Mean ± SEM the relative fold change using the 2ΔCt method (see Methods section). The 18S ribosomal RNA gene was used as an internal control for the normalization and gene expression of the operant saccharine self-administration group, which was used as the control (calibrator). (A) Ethanol increased the expression of the DNA methyltransferase genes, and topiramate or cocaine blocked this effect. (B) No changes were observed in the expression of carbonic anhydrase enzymes type II and IV (Ca2 and Ca4), but cocaine increased the gene expression of the kainate receptor containing the GluK1 subunit (Grik1). (C) Dnmt1 DNA methyltransferase corepressors showed heterogeneous results. Gene expression of Hdac2 increased after cocaine treatment, and Dmap1 increased after ethanol self-administration. (D) Ethanol increased the gene expression of the enzyme that methylates tRNA (Trdmt1, formerly known as Dnmt2). (E) The co-administration of topiramate and cocaine increased Drd2, Th and Oprm1 gene expression and cocaine alone increased the Oprm1 gene expression. *P < 0.01 compared with the saccharine-control group. #P < 0.01 compared with the ethanol group. &P < 0.01 compared with the topiramate + cocaine group.