INVOLVEMENT OF NITRIC-OXIDE IN NITROUS-OXIDE ANXIOLYSIS IN THE ELEVATED PLUS-MAZE

We recently reported that inhibition of nitric oxide (NO) production b y the NO synthase NOS) inhibitor L-N-G-nitro arginine (L-NOARG) antago nized the behavioral effects of a benzodiazepine (BZ) in a mouse parad igm for screening anxiolytic drug activity. Because other research has found that the anesthetic gas nitrous oxide (N2O) also produces BZ-li ke behavioral effects, the present research was conducted to ascertain whether NO might also be involved in N2O anxiolysis. Male Swiss-Webst er mice were tested in an elevated plus-maze inside an inflatable glov ebag. Exposure to N2O significantly increased exploratory activity on the open arms of the plus-maze, as measured by the number of entries i nto the open arms and the time spent on the open arms. Pretreatment wi th L-NOARG significantly reduced the N2O-induced elevation in open arm activity. This antagonism of the N2O effect was reversed by ICV treat ment of L-NOARG-pretreated mice with L-arginine but not D-arginine. Th ese findings indicate that NO possibly mediates behavioral effects of N2O in an animal model for anxiety.