Cocaine is an indirect dopamine agonist and upregulates dopamine-mediated glutamatergic transmission in the dorsal striatum. In this study, phosphorylation of N-methyl- D-aspartate (NMDA) NR1 subunits, extracellular signal-regulated kinase 1/2 (ERK1/2), and cyclic AMP response element-binding protein (CREB) and expression of c-Fos were simultaneously examined to understand an NMDA-dependent ERK1/2 pathway in striatal neurons of rats treated with acute cocaine. The data demonstrated that intraperitoneal (i.p.) injection of acute cocaine (20 mg/kg) significantly increased the immunoreactivity of phosphorylated (p)NMDA NR1 subunits on serine 896 and 897 in the dorsal striatum. Similarly, pERK1/2, pCREB and c-Fos immunoreactivities also were increased in the dorsal striatum after acute cocaine injection. These data suggest that acute injection of cocaine are necessary for activating NMDA receptors, which in turn stimulates an ERK1/2 signaling pathway leading to CREB phosphorylation and c-Fos expression in the dorsal striatum.

Keywords: MAP kinase, dopamine receptor, psychostimulant