Changes in ERK1/2 phosphorylation in the rat striatum and medial prefrontal cortex following administration of the adenosine A receptor agonist and antagonist.

The extracellular signal-regulated kinase (ERK) is enriched in the central nervous system, including the dopamine responsive regions such as the striatum and medial prefrontal cortex (mPFC). The kinase is sensitive to changing cellular and synaptic input and is implicated in the regulation of synaptic transmission and plasticity. In this study, the role of a G protein-coupled adenosine A receptor in the regulation of ERK1/2 was investigated in the rat brain in vivo. We found that an A agonist CPA after an intraperitoneal injection reduced ERK1/2 phosphorylation in the nucleus accumbens (NAc) and mPFC. In contrast, a single dose of an A antagonist DPCPX induced a rapid and transient increase in ERK1/2 phosphorylation in the caudate putamen (CPu), NAc, and mPFC. Pretreatment with a dopamine D receptor antagonist SCH23390 abolished the DPCPX-induced ERK1/2 phosphorylation in the striatum and mPFC. Coadministration of DPCPX and a D agonist SKF81297 at a low dose induced a greater elevation of ERK1/2 phosphorylation. Activation or blockade of A receptors had no effect on total ERK1/2 expression in the striatum and mPFC. These results reveal an existence of an inhibitory linkage from adenosine A receptors to ERK1/2 in striatal and mPFC neurons. This inhibitory linkage seems to form a dynamic balance with positive dopamine D receptor signaling to control the ERK1/2 pathway.