Nitrous oxide (N2O) increases brain L‐arginine in production of its antinociceptive effect in mice

Abstract

C57BL/6 (C57) inbred mice respond to N2O with an increase in brain nitric oxide synthase (NOS) activity and a robust antinociceptive effect; DBA/2 (DBA) fail to exhibit these responses (Ishikawa and Quock, Brain Res. 976:262–263, 2003a). This study was conducted to determine whether increasing the availability of nitric oxide (NO) by administration of L‐arginine might increase responsiveness of DBA mice to N2O and ascertain the effect of N2O on brain levels of L‐arginine. Sensitivity to N2O was assessed using the acetic acid‐induced abdominal constriction test. Whole brain levels of L‐arginine were quantified by HPLC. Intracerebroventricular preloading of L‐arginine in subthreshold doses enhanced the N2O‐induced antinociceptive effects in both C57 and DBA mice. A 60‐min exposure to 70% N2O produced a 12‐fold increase in brain L‐arginine levels of C57 mice, compared to room air exposure. Similar treatment of DBA mice resulted in a 5‐fold increase in brain L‐arginine levels. While the cause of the differential responsiveness of inbred mice to N2O remains to be determined, it is apparent that N2O increases brain L‐arginine levels to produce its antinociceptive effect. (Supported in part by NIH Grant GM‐77153 and the Allen I. White Distinguished Professorship.)