Halothane and desflurane requirements in alcohol-tolerant and -nontolerantrats

On the basis of data implicating GABAA receptors in the effects of volatile general anaesthetics, we hypothesized that alcohol-, barbiturate-, and ben zodiazepine-sensitive alcohol-nontolerant (ANT) rats would also be more sen sitive than alcohol-tolerant (AT) rats to two clinical general anaesthetics with differing potencies, halothane and desflurane. The obtunding effect o f halothane and desflurane on mature ANT (n = 17) and AT (n = 16) rats was assessed by the loss-of-righting reflex endpoint. ANT rats were significant ly (P < 0.0001) more sensitive to the obtunding effects of both halothane a nd desflurane (ED50 = 0.45+/-0.03% atm for ANT vs 0.95 +/- 0.04% atm for AT and 2.16 +/- 0.17 vs 3.69 +/- 0.13% arm, respectively). The immobilization effect of halothane and desflurane was assessed with the tail clamp/withdr awal endpoint. ANT rats were more sensitive to the effects of halothane (ED 50 = 1.10 +/- 0.08% atm for ANT vs 1.72 +/- 0.09% arm for AT; P < 0.0001) b ut not desflurane (ED50 = 6.25 +/- 0.25% atm for ANT vs 5.85 +/- 0.21% atm for AT). The data presented support the hypothesis that volatile anaestheti cs interact with specific neuronal proteins (possibly GABAA receptors) and agree with recent hypotheses that different elements of the anaesthetic sta te are produced by separate sites or mechanisms.