N-methyl-D-aspartate receptors and P38 mitogen-activated protein kinase are required for cAMP-dependent cyclase response element binding protein and ELK-1 phosphorylation in the striatum

In vivo cyclic adenosine monophosphate (cAMP)-induced N-methyl-D-aspartate receptor and mitogen-activated protein kinase activation was investigated i n the dorsal striatum by semiquantitative immunocytochemistry. Intracerebro ventricular infusion of 8-bromo-adenosine 3',5'-cyclic monophosphorothioate , Sp isomer (Sp-8-Br-cAMPS), increased phosphorylated cAMP-responsive eleme nt binding protein, phosphorylated Elk-1 and Fos immunoreactivity in a dose -dependent manner. Intracerebroventricular infusion of the N-methyl-D-aspar tate antagonist, MK801, decreased, but tetrodotoxin or the mitogen-activate d extracellular-regulated kinase inhibitor, PD98059, did not affect Sp-8-Br -cAMPS-induced phosphorylated c-AMP-responsive element binding protein, pho sphorylated Elk-1, phosphorylated extracellular-signal-regulated kinase and Fos immunoreactivity. The p38 mitogen-activated protein kinase inhibitor, SB203580, decreased the Sp-8-Br-cAMPS-induced increase in all markers, exce pt phosphorylated extracellular-signal-regulated kinase, in a dose-dependen t manner. We suggest that N-methyl-D-aspartate receptors couple c-AMP to phosphorylat ion events and immediate early gene induction in the nucleus of striatal me dium spiny neurons. These events are mediated by crosstalk between protein kinase A and mitogen-activated protein kinase cascades in vivo. (C) 2000 IB RO. Published by Elsevier Science Ltd. All rights reserved.