INTRATHECALLY ADMINISTERED NMDA RECEPTOR ANTAGONISTS REDUCE THE MAC OF ISOFLURANE IN RATS

Purpose: We studied the effects of intrathecal administration of an N- methyl-D-aspartate (NMDA) receptor antagonist and art antagonist of th e glycine site of the NMDA receptor on the minimum alveolar anaestheti c concentration (MAC) of isoflurane in rats, and on locomotor activity in conscious rats. Methods: In Wistar rats fitted with indwelling int rathecal catheters, we determined the MAC of isoflurane after the admi nistration of saline (control group); the competitive NMDA receptor an tagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosponic acid(CPP) at 0. 01, 0.1, and 1.0 nM; and the selective antagonist of the glycine sire on the NMDA receptor complex 7-chlorokynurenic acid (7CKA) at 0.1, 1.0 , and 10 nM. After measurement of MAC following administration of the antagonist, the equipotent reversal doss of NMDA of D-serine was admin istered The rats were examined for the presence of locomotor dysfuncti on by intrathecal administration of NMDA receptor antagonists, NMDA an d D-serine in conscious mts. Ail of the experiments were performed usi ng randomization and masking of drugs. Results: CPP at 0.1 and 1.0 nM decreased the MAC of isoflurane by 9.9-17.6% (P < 0.05). 7CKA at 1.0 a nd IO nM reduced MAC from 10.5-15.5% (P < 0.05). Intrathecal administr ation of NMDA or D-serine reversed the decreases in MAC to control val ues. Locomotor activity was not changed. Conclusions: We believe that NMDA receptor plays an important role in determining the MAC of isoflu rane in the spinal cord.