Figure 3 Quantification of cells expressing MeCP2 in response to the activation or overSelleckchem Carboplatin expression of PKG in the VTA. Quantification was carried out in (A) the dorsal CPu, (B) the NAc shell, and (C) the PFCx (n = 3 in the groups that were injected with KT5823 and … Effect of PKG activation and overexpression on HDAC2 expression in cocaine-treated rats Quantitative analysis of cells expressing HDAC2 in the dorsal CPu, NAc shell, and PFCx in response to intra-CPu injection of the plasmids and of Br-cG is shown in Figure 4. Inhibitors,research,lifescience,medical Data were obtained from immunohistochemistry experiments of coronal sections adjacent to those taken

for measuring MeCP2 levels. As was the case for MeCP2, HDAC2 levels were not modified by the cocaine injection. When Br-cG was microinjected into the CPu, HDAC2 levels were Inhibitors,research,lifescience,medical decreased by about 50% in CPu and PFCx and by about 40% in the NAc. The reduction was completely reversed when the selective PKG inhibitor was injected

before Br-cG. Figure 4 Quantification of cells expressing HDAC2 in response to the activation or overexpression of PKG in the CPu. Quantification was carried out in (A) the dorsal CPu, (B) the NAc shell, Inhibitors,research,lifescience,medical and (C) the PFCx (n = 3 in the groups that were injected with KT5823 and … In the PFCx, and to a lesser degree in the CPu and NAc, activation by Br-cG of the exogenous kinase resulted in a significant inhibition of HDAC2 expression, but the overexpression of the kinase by itself did not reduce levels of the deacetylase (Fig. 4). Again, the effects of the activation/overexpression were totally blocked Inhibitors,research,lifescience,medical by the injection of KT5823. Figure 5 shows quantitative analysis of HDAC2 expression in the dorsal CPu, NAc shell, and PFCx in response to intra-VTA injections. As was the case for MeCP2 expression, HDAC2 levels were not modified. Figure 5 Quantification Inhibitors,research,lifescience,medical of cells expressing HDAC2 in response to the activation or overexpression of PKG in the VTA. Quantification was carried out

in (A) the dorsal CPu, (B) the NAc shell, and (C) the PFCx (n = 3 in the groups that were injected with KT5823 and … Illustration of the PKG effects on MeCP2 and HDAC2 expression Figure 6 illustrates MeCP2 and HDAC2 immunostaining in the dorsal CPu of rats that received intra-CPu injections, according to the schedule shown in Figure 1. Both MeCP2 and HDAC2 immunoreactivities were exclusively found in cell nuclei, as expected for proteins science that bind DNA or histones. Overexpression of the kinase alone reduced MeCP2 and HDAC2 labeling. Activation of endogenous plus overexpressed kinase reduced the labeling further. The reduction in protein expression was reversed by KT5823, and there was an increase in the number of immunoreactive cells; the labeling intensity of both proteins was somewhat enhanced. Figure 6 Photomicrographs showing (A) MeCP2 and (B) HDAC2 immunoreactivity in response to the activation or overexpression of PKG in the CPu.