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The interaction between nitrous oxide and isoflurane on suppression of learning: a study using classical conditioning
H M El-Zahaby1, M M Ghoneim, R I Block
1Department of Anesthesia, College of Medicine, University of Iowa, Iowa City, USA.
Background:
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).
Methods:
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).
Results:
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.
Conclusions:
N2O and isoflurane interact additively on suppression of learning.