Increasing the availability of nitric oxide (NO) increases sensitivity of nitrous oxide (N2O)‐insensitive inbred mice to N2O‐induced antinociception

Abstract

N2O‐induced antinociception in mice is dependent on the neuromodulator NO. In contrast to C57BL/6 mice, DBA/2 mice fail to respond to N2O with a robust antinociceptive response or with an increase in brain nitric oxide synthase (NOS) enzyme activity, suggesting that failure of DBA/2 mice to respond to N2O might result from a deficit of NO function (Ishikawa and Quock, Brain Res. 976:262–263, 2003). Therefore, it was of interest to determine whether increasing the availability of NO might increased sensitivity of DBA mice to N2O. Male DBA/2 mice (20–25 g) were pretreated with sub‐antinociceptive intracerebroventricular doses of the NO donor 3‐morpholinosydnoimine (SIN‐1) or the NO precursor L‐arginine (L‐Arg) then assessed for responsiveness to N2O‐induced antinociception using the acetic acid abdominal constriction test. Both pretreatments increased the antinociceptive responsiveness of DBA/2 mice to N2O. These results show that the NOS enzyme in DBA/2 mice is functional and that the deficit in NO function that obstructs sensitivity to N2O‐induced antinociception may lie in some other component or function related to NO. (Supported in part by NIH Grant GM‐77153).