Halothane and desflurane requirements in alcohol-tolerant and -nontolerant rats

On the basis of data implicating GABAA receptors in the effects of volatile general anaesthetics, we hypothesized that alcohol-, barbiturate-, and benzodiazepine-sensitive alcohol-nontolerant (ANT) rats would also be more sensitive than alcohol-tolerant (AT) rats to two clinical general anaesthetics with differing potencies, halothane and desflurane. The obtunding effect of 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 significantly (P < 0.0001) more sensitive to the obtunding effects of both halothane and 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% atm, respectively). The immobilization effect of halothane and desflurane was assessed with the tail clamp/withdrawal endpoint. ANT rats were more sensitive to the effects of halothane (ED50 = 1.10 +/- 0.08% atm for ANT vs 1.72 +/- 0.09% atm for AT; P < 0.0001) but 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 anaesthetics interact with specific neuronal proteins (possibly GABAA receptors) and agree with recent hypotheses that different elements of the anaesthetic state are produced by separate sites or mechanisms.