INHIBITORS OF NITRIC-OXIDE SYNTHESIS ANTAGONIZE NITROUS-OXIDE ANTINOCICEPTION IN MICE AND RATS

Administration of the anesthetic gas N2O evoked an antinociceptive eff ect in two rodent antinociception paradigms. In the mouse abdominal co nstriction test, pretreatment with the nitric oxide synthase (NOS) inh ibitor L-N-G-nitroarginine (L-NOARG) caused dose-related antagonism of the antinociceptive effect of N2O but not of either morphine or l-N-[ 2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide methane sulfonate. This antinociceptive effect was also antagonized by systemic pretreatment w ith the NOS inhibitors L-N-G-nitroarginine methyl ester (L-NAME) and L -N-G-monomethylnitroarginine. The antagonism of N2O by L-NOARG and L-N AME was completely reversed by i.c.v. administration of L-arginine but not D-arginine. In the absence of NOS inhibition, N2O antinociception was potentiated by i.c.v. treatment with L-arginine but not D-arginin e. The i.c.v. pretreatment with L-NAME also reduced N2O antinociceptio n; this antagonism was also stereospecifically reversed by L-arginine. In the rat hot plate test, the antinociceptive response to 70% N2O wa s antagonized in dose-related manner by i.c.v. pretreatment with L-NOA RG or L-NAME. N2O antinociception was restored by i.c.v. treatment wit h L-arginine but not D-arginine. However, neither L-arginine nor D-arg inine alone affected N2O antinociception. These results implicate a ke y role for NO in the mediation of the antinociceptive effects of N2O i n both mice and rats.