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Intrathecally administered NMDA receptor antagonists reduce the MAC of isoflurane in rats
K Ishizaki1, N Yoshida, D M Yoon
1Department of Anesthesiology and Reanimatology, School of Medicine, Gunma University, Japan.
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)propyl-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.
Insights
NMDA receptor antagonists reduced isoflurane MAC in rats, indicating their role in spinal anesthesia. NMDA or D-serine reversed these effects without impacting locomotor activity.
Area of Science:
- Neuroscience
- Anesthesiology
Background:
- The N-methyl-D-aspartate (NMDA) receptor is implicated in various neurological processes.
- Understanding its role in anesthesia is crucial for developing targeted interventions.
Purpose of the Study:
- To investigate the effect of NMDA receptor antagonists on the minimum alveolar anesthetic concentration (MAC) of isoflurane in rats.
- To assess the impact of these antagonists on locomotor activity.
Main Methods:
- Wistar rats received intrathecal administration of NMDA receptor antagonists (CPP, 7CKA) or saline.
- MAC of isoflurane was determined, followed by administration of NMDA or D-serine.
- Locomotor activity was evaluated in conscious rats.
Main Results:
- CPP and 7CKA significantly decreased isoflurane MAC.
- NMDA or D-serine administration reversed the MAC reduction to baseline levels.
- No significant changes in locomotor activity were observed.
Conclusions:
- NMDA receptors in the spinal cord play a significant role in modulating the MAC of isoflurane.
- Targeting NMDA receptors may offer novel strategies for spinal anesthesia.
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