Chronic Exposure to Nitrous Oxide Increases [³H]MK801 Binding in the Cerebral Cortex, but Not in the Hippocampus of Adult Mice

Abstract

Chronic exposure of adult mice to inhalational anesthetic nitrous oxide (N2O) results in anesthetic tolerance. N2O is an NMDA (N‐methyl‐d‐aspartate) antagonist. It has been demonstrated that chronic administration of members of the NMDA antagonist class of drugs (e.g., MK801) causes upregulation of NMDA receptors in certain brain regions that could, at least in part, explain the development of tolerance. We sought to determine whether the anesthetic tolerance resulting from chronic exposure to N2O reflects changes in the number and/or distribution of NMDA receptors. We exposed mice to either a 50‐ or 75‐vol% N2O atmosphere continuously for 1 or 2 weeks and performed binding studies with [3H]MK801 and NR1 antibodies. Binding studies revealed a significant (P < 0.05) increase in [3H]MK801 binding in the cerebral cortex after 2 weeks of N2O (50‐ and 75‐vol%) exposure. Immunocytochemical binding of NR1 antibodies in selected brain regions showed no changes in distribution pattern. The timing of this increase in [3H]MK801 binding correlates with the time period required for development of tolerance.