Exposure to nitrous oxide stimulates a nitric oxide-dependent neuronal release of β-endorphin in ventricular-cisternally-perfused rats

We have previously shown that the antinociceptive effect of nitrous oxide (N2O) in the rat hot plate test is sensitive to antagonism by antisera against the endogenous opioid peptide β-endorphin. Moreover, N2O-induced antinociception is reduced by inhibition of nitric oxide (NO) production in the brain. To test the hypothesis that N2O might stimulate an NO-dependent neuronal release of β-endorphin, we conducted a ventricular-cisternal perfusion with artificial cerebrospinal fluid (aCSF) in urethane-anesthetized Sprague–Dawley rats. Ten-minute fractions of aCSF perfusate were collected from separate groups of room air-exposed rats, N2O-exposed rats, and L-NAME-pretreated, N2O-exposed rats; they were then analyzed for their content of NO metabolites and β-endorphin. Compared to room air control, exposure to 70% N2O increased perfusate levels of the NO metabolites nitrite and nitrate as well as β-endorphin. Pretreatment of rats with L-NG-nitro arginine methyl ester, an inhibitor of NO synthase, prevented the N2O-induced increases in nitrite, nitrate and β-endorphin. These findings demonstrate in an in vivo rat model that N2O may stimulate an NO-dependent neuronal release of β-endorphin.