Activation of Protein Kinases and Phosphatases Coupled to Glutamate Receptors Regulates the Phosphorylation State of DARPP32 at Threonine 75 After Repeated Exposure to Cocaine in the Rat Dorsal Striatum in a Ca2+-Dependent Manner.

BACKGROUND:Phosphorylation state of dopamine- and cAMP-regulated phosphoprotein, molecular weight 32 kDa is crucial to understand drug-mediated synaptic plasticity. In this study, mechanisms underlying repeated cocaine-stimulated phosphorylation of at threonine 75 were determined by investigating the hypothesis that activation of protein kinases and phosphatases coupled to glutamate signaling is necessary for the regulation of after repeated cocaine administration. METHODS:Intracaudate drug infusions into the rat dorsal striatum followed by Western immunoblot analysis were mainly performed to test this hypothesis. RESULTS:The results demonstrated that 7 repeated daily intraperitoneal injections of cocaine (20mg/kg) upregulated the expression of Increases in the cytosolic Ca(2+) concentrations followed by Ca(2+)-dependent protein kinase activation through stimulation of Ca(2+) channels in striatal neurons were necessary for the phosphorylation. Activation of protein phosphatases further regulated the phosphorylation state by deactivating pDduanyu37P32-Thr75 and upstream protein kinases. CONCLUSION:These findings suggest that activation of protein kinases and phosphatases coupled to glutamate receptors controls the phosphorylation state of after repeated exposure to cocaine in the dorsal striatum in a Ca(2+)-dependent manner.

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