EFFECT OF LOW AND HIGH-DOSES OF NITROUS-OXIDE ON PREPROENKEPHALIN MESSENGER-RNA AND ITS PEPTIDE METHIONINE-ENKEPHALIN LEVELS IN THE HYPOTHALAMUS

The effect of exposure to nitrous oxide (N2O) on the levels of preproe nkephalin mRNA in the hypothalamus of rats was examined. In the first experiment, rats were exposed to 1000 ppm N2O for 8 h a day over 4 day s. Compared with controls (which were exposed to air over the same dur ation), the N2O exposed animals exhibited significant elevations in pr eproenkephalin mRNA levels in the hypothalamus. In a second experiment , rats were exposed to 60% N2O or air for 12, 24 and 48 h duration, an d hypothalamic levels of preproenkephalin mRNA as well as methionine e nkephalin were analyzed. Compared with controls, N2O exposed rats exhi bited significant elevations in preproenkephalin mRNA levels. The leve ls on preproenkephalin mRNA were significantly higher after 48 h of N2 O exposure than after 12 h of N2O exposure. Similarly, the concentrati on of methionine enkephalin was significantly higher after 24 and 48 h of exposure to N2O than after exposure to 12 h of N2O or air. These r esults indicate that (a) exposure to N2O results in significant elevat ions in preproenkephalin mRNA levels, (b) the increased preproenkephal in mRNA levels appear to be proportional to the concentration of N2O e xposure as well as the duration of N2O exposure, and (c) N2O-induced e levation in preproenkephalin mRNA levels is associated with correspond ing increase in tissue concentrations of methionine enkephalin. In tot al, these results suggest that N2O selectively stimulates synthesis of methionine enkephalin in the diencephalic region of the brain.