Nitrous oxide-induced NO-dependent neuronal release of β-endorphin from the rat arcuate nucleus and periaqueductal gray

Nitrous oxide (N2O)-induced antinociception is thought to result from nitric oxide (NO)-dependent neuronal release of endogenous opioid peptides in the central nervous system. The present study employed microdialysis to determine whether exposure to N2O stimulates proopiomelanocortin (POMC) neurons to release β-endorphin in the arcuate nucleus (ARC) of the hypothalamus and the periaqueductal gray (PAG) of the midbrain. Male Sprague–Dawley rats were stereotaxically implanted with microdialysis probes in the ARC or PAG. Exposure to 70% N2O significantly increased dialysate levels of oxidation products of NO as well as β-endorphin, compared to levels in fractions collected under room air. These increases in the ARC and PAG were abolished by systemic pretreatment with l-NG-nitro arginine methyl ester (l-NAME). These findings suggest an association between increased NO activity and the stimulated release of β-endorphin during exposure of rats to N2O.

Research Highlights
► N2O increases extracellular levels of nitrite and nitrate in the ARC and PAG.
► N2O increases extracellular levels of β-endorphin in the ARC and PAG.
► These increases are both reversed by pretreatment with a NOS-inhibitor.