Abstract
Purpose
We studied the effects of intrathecal administration of an N-methyl-D-aspartate (NMDA) receptor antagonist and an antagonist of the glycine site of the NMDA receptor on the minimum alveolar anaesthetic concentration (MAC) of isoflurane in rats, and on locomotor activity in conscious rats.
Methods
In Wistar rats fitted with indwelling intrathecal catheters, we determined the MAC of isoflurane after the administration of saline (control group); the competitive NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)pro-pyl-1-phosponic acid(CPP) at 0.01, 0.1, and 1.0 nM; and the selective antagonist of the glycine site 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 dose of NMDA or D-serine was administered. The rats were examined for the presence of locomotor dysfunction by intrathecal administration of NMDA receptor antagonists, NMDA and D-serine in conscious rats. All of the experiments were performed using 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 and 10 nM reduced MAC from 10.5–15.5% (P < 0.05). Intrathecal administration of NMDA or D-serine reversed the decreases in MAC to control values. Locomotor activity was not changed.
Conclusions
We believe that NMDA receptor plays an important role in determining the MAC of isoflurane in the spinal cord.
Résumé
Objectif
Étudier l’influence de l’administration d’un antagoniste du récepteur N-méthyl-D-aspartate (NMDA) et d’un antagoniste du site glycine du NMDA sur la concentration anesthésique alvéolaire minimum (MAC) de l’isoflurane chez le rat anesthésié et sur l’activité locomotrice chez le rat conscient.
Méthodes
Chez des rats Wistar porteurs d’un cathéter sousarachnoïdien implantés, nous avons déterminé le MAC après l’administration de soluté physiologique (groupe contrôle); de l’antagoniste compétitif du récepteur NMDA. l’acide 3-(2-car-boxyperazine-4-yl) propyl-l-phosphonique (CPP) à 0,01, 0,1 et 1,0 nM; et l’antagoniste sélectif du site glycine du complexe récepteur NMDA l’acide 7-chlorokynurénique (7CKA) à 0,1 1,0 et 10 nM. Après la mesure du MAC à la suite de l’administration de l’antagoniste, des doses de neutralisation équipotentes de NMDA ou de D-sérine ont été administrées. La présence d’un dysfonctionnement locomoteur a été recherchée par l’administration sousarachoïdienne de l’antagoniste du récepteur NMDA, de NMDA et de D-sérine chez les rats conscients. Toutes les expériences ont été conduites aléatoirement et avec masquage des produits.
Résultats
Le CPP à 0,1 et 1,0 nM a diminué le MAC de l’isoflurane de 9,9–17.6% (P < 0,05). Le 7CKA à 1,0 et 10 nM a réduit le MAC de 10,5–15,5% (P < 0,05). Administration sousarachnoïdienne de NMDA ou de D-sérine a ramené le MAC aux valeurs de contrôle. L’activité locomotrice n’a pas changé.
Conclusion
Nous croyons que le récepteur NMDA joue au niveau de la moelle épinière un rôle important dans la délimination du MAC.
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Ishizaki, K., Yoshida, N., Yoon, D.M. et al. Intrathecally administered NMDA receptor antagonists reduce the MAC of isoflurane in rats. Can J Anesth 43, 724–730 (1996). https://doi.org/10.1007/BF03017958
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DOI: https://doi.org/10.1007/BF03017958