THE INTERACTION BETWEEN NITROUS-OXIDE AND ISOFLURANE ON SUPPRESSION OF LEARNING - A STUDY USING CLASSICAL-CONDITIONING IN RABBITS

Background: Nitrous oxide (N2O) is commonly combined with a volatile a gent for administration of general anesthesia. We studied the effects of N2O and isoflurane on learning of the rabbit nictitating membrane r esponses (NMRs). Methods: Classical conditioning of the NMR was accomp lished by presenting a 400 ms tone conditioned stimulus before the pre sentation of a 100 ms shock unconditioned stimulus over 6 daily traini ng sessions. The percentages of conditioned responses (CRs) were calcu lated 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 l earning for each drug were calculated. Percentages of CRs were calcula ted for treatments with combinations of 0.2% isoflurane with either 32 or 48% N2O (n=14, for each). Results: Isobolographic analysis demonst rated that the combination of the two drugs exerted no greater effect than that seen with either agent administered alone; for well-establis hed CRs (mean of days 5 and 6), the estimated concentrations correspon ding 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. Conc lusions: N2O and isoflurane interact additively on suppression of lear ning.