Both cerebral GABA(A) receptors and spinal GABA(A) receptors modulate the capacity of isoflurane to produce immobility

We previously demonstrated that intrathecal administration of the noncompet itive gamma -aminobutyric acid type A (GABA(A)) receptor antagonist picroto xin increased isoflurane MAC (the minimum alveolar concentration of anesthe tic producing immobility in 50% of animals) by a maximum (ceiling effect) o f approximately 40%. We also found that IV administration of picrotoxin inc reased MAC by more than 60%, without evidence of a ceiling effect. The larg er increase with TV administration suggested a role of cerebral GABA(A) rec eptors. Accordingly, in this study we examined the effect of intracerebrove ntricular administration of picrotoxin in rats, finding that picrotoxin inf usion into the third ventricle increased isoflurane MAC by a maximum of app roximately 40%, without finding a ceiling effect. In addition, we concurren tly infused picrotoxin into the intrathecal and intracerebroventricular spa ces, producing an increase in MAC in excess of 70%, also with no evidence o f a ceiling effect. The dose-response relationship for the intrathecal-intr aventricular infusion paralleled that of the IV infusion but was shifted to the left by an order of magnitude. We conclude that both cerebral and spin al GABA(A) receptors modulate the capacity of inhaled anesthetics to produc e immobility. Because other studies have shown that the spinal cord, and no t the brain, mediates the capacity of inhaled anesthetics to produce immobi lity, these results call into question the relevance of GABA(A) receptors t o the immobilizing action of isoflurane.