symptom counts. In cultured mouse cortical neurons, chronic ethanol was reported to induce demethylation of CpG islands of the NMDA receptor subunit gene nr2b with a concomitant increase in nr2b expression (Marutha Ravindran and Ticku, 2005). Methylation of the protein phosphatase 1 gene pp1 and demethylation of the reelin gene reln (encoding a protein necessary for neuronal cell signaling) in the mouse hippocampus were reported to change after one hour in response to fear conditioning (Miller and Sweatt, 2007). Expression of cFos, bdnf, and cdk5 are increased by cocaine; a single cocaine injection was reported to cause chromatin remodeling at the cFos promoter in rat striatum, and at the bdnf, and cdk5 promoters after chronic cocaine administration (Kumar et al, 2005). Murine studies suggest that remodeling by chronic cocaine administration was through a decrease in the histone deacetylase HDAC5 function (Renthal et al, 2007). In rats, cocaine administration produced decreased histone methylation in the prefrontal cortex (Black et al, 2006). Maternal cocaine administration in rats increased methylation at a CpG site in the promoter of the protein kinase Cε (PKCε) gene in fetal heart, and decreased PKCε mRNA and protein levels, presumably through a decrease in Ap1 transcription factor binding
