EFFECT OF ELIPRODIL, AN NMDA RECEPTOR ANTAGONIST ACTING AT THE POLYAMINE MODULATORY SITE, ON LOCAL CEREBRAL GLUCOSE USE IN THE RAT-BRAIN

The present investigation examined the effect of eliprodil, an atypica l NMDA receptor antagonist that acts at the polyamine modulatory site, on local cerebral glucose utilization using the quantitative autoradi ographic 2-[C-14]deoxyglucose method in the conscious rat. Eliprodil, at doses of 3, 10 and 30 mg/kg i.p., did not increase cerebral glucose use in any of the 82 different brain regions studied. However, in som e of the regions examined, local cerebral glucose utilization was slig htly reduced, the most pronounced decreases being measured in some ext rapyramidal, sensorimotor and limbic areas (dentate gyrus, septum, lat eral habenula, amygdala). This decrease in glucose utilization was dos e-dependent: no significant change was noted after 3 mg/kg i.p. of eli prodil, while 18 (at 10 mg/kg, i.p.) and 29 (at 30 mg/kg, i.p.) region s displayed a moderate (20-25%) though significant decrease in glucose use. These data demonstrate that the pattern of alterations in glucos e use produced by eliprodil is different from that induced by NMDA cha nnel blockers or competitive NMDA receptor antagonists. The fact that blockade of the polyamine modulatory site is not associated with an ac tivation of specific limbic circuits may explain why, at neuroprotecti ve doses, eliprodil is devoid of those unwanted side effects (includin g intrinsic neurotoxicity on cortical neurons) associated with NMDA ch annel blockers.