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

作者：Kim Jieun; Ryu In Soo; Seo Su Yeon; Choe Eun Sang^*

来源：International Journal of Neuropsychopharmacology, 2015, 18(12): UNSP pyv075.

DOI：10.1093/ijnp/pyv075

• DARPP32
• glutamate
• phosphorylation and dephosphorylation
• psychostimulant
• striatum

Background: Phosphorylation state of dopamine-and cAMP-regulated phosphoprotein, molecular weight 32 kDa (DARPP32) is crucial to understand drug-mediated synaptic plasticity. In this study, mechanisms underlying repeated cocaine-stimulated phosphorylation of DARPP32 at threonine 75 (pDARPP32-Thr75) were determined by investigating the hypothesis that activation of protein kinases and phosphatases coupled to glutamate signaling is necessary for the regulation of pDARPP32-Thr75 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 (20 mg/kg) upregulated the expression of pDARPP32-Thr75. Increases in the cytosolic Ca2+ concentrations followed by Ca2+-dependent protein kinase activation through stimulation of Ca2+ channels in striatal neurons were necessary for the phosphorylation. Activation of protein phosphatases further regulated the phosphorylation state by deactivating pDARPP32-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 DARPP32-Thr75 after repeated exposure to cocaine in the dorsal striatum in a Ca2+ dependent manner.

• 出版日期2015-11