BACKGROUND: Nitrous oxide is a commonly used anesthetic that inhibits the activity of methionine synthase, an enzyme involved in methylation reactions and DNA synthesis and repair. This inhibition triggers vacuole formation and degeneration of neurons in areas of the developing and mature brain that are important for spatial memory, raising the possibility that nitrous oxide might have sustained effects on learning. METHODS: To test this possibility, we randomized 18-month-old Fischer 344 rats (n � 13 per group) to 4hof70%nitrous oxide � 30 % oxygen or 70 % nitrogen � 30% oxygen (control) and assessed memory using a 12-arm radial maze for 14 days beginning 2 days after nitrous oxide inhalation. In separate, identically treated groups of rats, we measured methionine synthase activity in the cortex and liver at the end of nitrous oxide exposure and 2 days later (n � 3 rats per group per time point) using a standard assay. RESULTS: Liver and cortical methionine synthase was inhibited during nitrous oxide inhalation (6 % and 23 % of control in liver and cortex, respectively; P � 0.01). Live
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