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GENERAL ARTICLES

Both Cerebral GABA_A Receptors and Spinal GABA_A Receptors Modulate the Capacity of Isoflurane to Produce Immobility

Department of Anesthesia and Perioperative Care, University of California, San Francisco, California

Address correspondence and reprint requests to James Sonner, MD, Department of Anesthesia, S-455, University of California, San Francisco, CA 94143-0464.

We previously demonstrated that intrathecal administration of the noncompetitive -aminobutyric acid type A (GABA_A) receptor antagonist picrotoxin increased isoflurane MAC (the minimum alveolar concentration of anesthetic producing immobility in 50% of animals) by a maximum (ceiling effect) of approximately 40%. We also found that IV administration of picrotoxin increased MAC by more than 60%, without evidence of a ceiling effect. The larger increase with IV administration suggested a role of cerebral GABA_A receptors. Accordingly, in this study we examined the effect of intracerebroventricular administration of picrotoxin in rats, finding that picrotoxin infusion into the third ventricle increased isoflurane MAC by a maximum of ap-proximately 40%, without finding a ceiling effect. In addition, we concurrently infused picrotoxin into the intrathecal and intracerebroventricular spaces, producing an increase in MAC in excess of 70%, also with no evidence of a ceiling effect. The dose-response relationship for the intrathecal-intraventricular infusion paralleled that of the IV infusion but was shifted to the left by an order of magnitude. We conclude that both cerebral and spinal GABA_A receptors modulate the capacity of inhaled anesthetics to produce immobility. Because other studies have shown that the spinal cord, and not the brain, mediates the capacity of inhaled anesthetics to produce immobility, these results call into question the relevance of GABA_A receptors to the immobilizing action of isoflurane.

Implications: In rats, cerebral -aminobutyric acid type A (GABA_A) receptors, in addition to spinal GABA_A receptors, influence the immobilizing action of isoflurane but are probably not responsible for that action.

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