EFFECTS OF NMDA RECEPTOR GLYCINE RECOGNITION SITE ANTAGONISM ON CEREBRAL METABOLIC-RATE FOR GLUCOSE AND CEREBRAL BLOOD-FLOW IN THE CONSCIOUS RAT

Glycine is a requisite cofactor for glutamatergic activation of the N- methyl-D-aspartate (NMDA) receptor. Antagonism of glutamate at the NMD A receptor has been shown to cause substantial changes in regional cer ebral metabolic rate for glucose utilization (CMRglu) and blood flow ( CBF). This study examined CMRglu and CBF changes caused by antagonism of glycine at the NMDA receptor recognition site. Rats were anesthetiz ed with halothane and vascular access was obtained. The animals were t hen awakened. One hour later, either vehicle (control) or ACEA 1021 (5 mg/kg followed by 3.5 mg.kg(-1).h(-1) or 10 mg/kg followed by 7 mg.kg (-1).h(-1)) was infused intravenously. CMRglu and CBF were then determ ined. Autoradiographic analysis of 25 regions revealed effects of ACEA 1021 on CMRglu in the frontal, sensory, parietal and auditory cortice s and the anteroventral and subthalamic nuclei. These changes deviated less than 15% from control. Effects on CBF were also small. The CMRgl u and CBF effects of ACEA 1021 are substantially less than those previ ously observed for either competitive or non-competitive glutamate NMD A antagonists. We conclude that inhibition of the NMDA glycine recogni tion site has little or no effect on CMRglu or CBF at the doses examin ed. This is consistent with the absence of psychotomimetic effects obs erved for this class of drugs. (C) 1998 Elsevier Science B.V.