dizocilpine-maleate and 8-bromoadenosine-3--5--cyclic-monophosphorothioate

In vivo cyclic adenosine monophosphate (cAMP)-induced N-methyl-D-aspartate receptor and mitogen-activated protein kinase activation was investigated in the dorsal striatum by semiquantitative immunocytochemistry. Intracerebroventricular infusion of 8-bromo-adenosine 3',5'-cyclic monophosphorothioate, Sp isomer (Sp-8-Br-cAMPS), increased phosphorylated cAMP-responsive element binding protein, phosphorylated Elk-1 and Fos immunoreactivity in a dose-dependent manner. Intracerebroventricular infusion of the N-methyl-D-aspartate antagonist, MK801, decreased, but tetrodotoxin or the mitogen-activated extracellular-regulated kinase inhibitor, PD98059, did not affect Sp-8-Br-cAMPS-induced phosphorylated c-AMP-responsive element binding protein, phosphorylated 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, except phosphorylated extracellular-signal-regulated kinase, in a dose-dependent manner. We suggest that N-methyl-D-aspartate receptors couple c-AMP to phosphorylation events and immediate early gene induction in the nucleus of striatal medium spiny neurons. These events are mediated by crosstalk between protein kinase A and mitogen-activated protein kinase cascades in vivo.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Animals; Cyclic AMP Response Element-Binding Protein; Dizocilpine Maleate; DNA-Binding Proteins; Enzyme Inhibitors; ets-Domain Protein Elk-1; Flavonoids; Imidazoles; Male; MAP Kinase Signaling System; Mitogen-Activated Protein Kinases; Neostriatum; Neurons; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-fos; Pyridines; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Sodium Channels; Tetrodotoxin; Thionucleotides; Transcription Factors