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 experimental evidence suggests that motor activity is modulated by striatal dopamine 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 NMDA or 50 mM KCl 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 KCl-evoked increase in extracellular DA. Infusion of NMDA or KCl led to a decrease in extracellular DOPAC, and HE did not modulate these effects. However, HE attenuated the NMDA- but not the KCl-induced reduction in extracellular HVA. The results point to the impairment of modulation of striatal DA discharge and metabolism by glutamate acting at NMDA receptors, contributing to the motor disturbances in HE.
Borkowska
H D
HD
Tampere Brain Research Center, University of Tampere Medical School, Finland.
Oja
S S
SS
Oja
O S
OS
Saransaari
P
P
Hilgier
W
W
Albrecht
J
J
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D006501:Hepatic Encephalopathy / Q000378:metabolism* / Q000503:physiopathology; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*
D018690:Excitatory Amino Acid Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D015102:3,4-Dihydroxyphenylacetic Acid; D016202:N-Methylaspartate; D011189:Potassium Chloride; D004298:Dopamine; D006719:Homovanillic Acid