Effects of Repeated Intermittent Exposures to Nitrous Oxide on Central Neurotransmitters and Hepatic Methionine Synthetase Activity in Cd-1 Mice

Abstract

The central neurotransmitters and hepatic methionine synthetase (MS) appear to play an important role in mediating the side effects associated with N2O exposure. Male CD-1 mice were exposed to 0, 50, 500, and 5,000 ppm of N2O 6 hr per day, 5 days a week for 2 or 13 weeks. One day after the last day of exposure, the animals were decapitated and steady state concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT), 3-methoxy-4-hydroxy-mandelic acid (VMA), 3-methoxy-4-hydroxyphenyl glycol (MOPEG), dihydroxphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) were determined in six discreet brain regions using electrochemical high-performance liquid chromatography. Hepatic MS activity was measured using a newly developed non-isotopic method. After a 2-week exposure to 5,000 ppm N2O, levels of NE and DA in some brain regions were significantly increased and were accompanied by significant decreases in the levels of their major metabolites. Serotonin levels were significantly decreased in certain brain regions. After the 13-week exposure to 5,000 ppm N2O, levels of NE, DA, and 5-HT significantly increased in the hypothalamus. Hepatic MS activity was not affected at any dose level of N2O used. The alterations in neurotransmitter levels may be related to the reported clinical and behavioral effects associated with N2O misuse or occupational exposures.