N-methyl-D-aspartate-evoked changes in the striatal extracellular levels of dopamine and its metabolites in vivo in rats with acute hepatic encephalopathy

Acute hepatic encephalopathy (HE) is associated with disturbances in motor functions, but the underlying mechanisms remain obscure. Considerable exper imental evidence suggests that motor activity is modulated by striatal dopa mine neurons whose discharge is under glutamatergic control, mostly through activation of N-methyl-D-aspartate (NMDA) receptors. In this study we used intrastriatal microdialysis to compare the effects of infusion of 10 mM NM DA or 50 mM KCI as a general release stimulus, on the extracellular levels of endogenous dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in control rats and in rats with acute HE induced by repeated administration of thioacetamide. The basal levels of DA and DOPAC were not significantly altered by HE, while the HVA level was reduced. HE did not significantly affect the NMDA-or KCI-evoked increase i n extracellular DA. Infusion of NMDA or KCI led to a decrease in extracellu lar DOPAC, and HE did not modulate these effects. However, HE attenuated th e NMDA- but not the KCI-induced reduction in extracellular HVA. The results point to the impairment of modulation of striatal DA discharge and metabol ism by glutamate acting at NMDA receptors, contributing to the motor distur bances in HE. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.