Epigenetic Effects Induced by Methamphetamine and Methamphetamine-Dependent Oxidative Stress

Figure 9

The effects of DRD1/PKA pathway on CDK5 and DARPP-32. In physiologic conditions, CDK5 phosphorylates DARPP-32 at Th75, thus softening the effects of PKA on DARPP-32. However, the abnormal phosphorylation of Thr34 carried out by enhanced DRD1/PKA cannot be counterbalanced by CDK5. This occurs since DRD1/PKA activates phosphatase PP2A, which inhibits the effects of CDK5 and enhances those of PKA. As a result, DARPP-32 phosphorylated at Thr34 increases and potentiates the inhibition of PP1.