Open AccessBoth Cerebral GABAA Receptors and Spinal GABAA Receptors Modulate the Capacity of Isoflurane to Produce Immobility
Author(s) -
Yi Zhang,
Caroline R. Stabernack,
James M. Sonner,
Robert C. Dutton,
Edmond I. Eger
Publication year - 2001
Publication title -
anesthesia and analgesia/anesthesia and analgesia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.404
H-Index - 201
eISSN - 1526-7598
pISSN - 0003-2999
DOI - 10.1097/00000539-200106000-00047
Subject(s) - picrotoxin , gabaa receptor , medicine , isoflurane , anesthesia , receptor , pharmacology , gaba receptor antagonist , anesthetic , endocrinology , bicuculline
We previously demonstrated that intrathecal administration of the noncompetitive gamma-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 approximately 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.