The interaction between nitrous oxide and isoflurane on suppression of learning: a study using classical conditioning in rabbits.

Abstract

Nitrous oxide (N2O) is commonly combined with a volatile agent for administration of general anesthesia. We studied the effects of N2O and isoflurane on learning of the rabbit nictitating membrane responses (NMRs). Classical conditioning of the NMR was accomplished by presenting a 400 ms tone conditioned stimulus before the presentation of a 100 ms shock unconditioned stimulus over 6 daily training sessions. The percentages of conditioned responses (CRs) were calculated for animals treated with 0% (n = 10), 33% (n = 11), 67% (n = 11), and 75% (n = 7) N2O and for those treated with 0% (n = 8), 0.2% (n = 7), 0.4%, (n = 13) and 0.8% (n = 9) isoflurane separately. ED-50 for suppression of learning for each drug were calculated. Percentages of CRs were calculated for treatments with combinations of 0.2% isoflurane with either 32 or 48% N2O (n = 14, for each). Isobolographic analysis demonstrated that the combination of the two drugs exerted no greater effect than that seen with either agent administered alone; for well-established CRs (mean of days 5 and 6), the estimated concentrations corresponding to a rate of 70% CRs were 0.31% isoflurane with no N2O, 65.3% N2O with no isoflurane, and 0.2% isoflurane combined with 32.4% N2O. N2O and isoflurane interact additively on suppression of learning.