Involvement of nitric oxide in nitrous oxide anxiolysis in the elevated plus-maze

We recently reported that inhibition of nitric oxide (NO) production by the NO synthase (NOS) inhibitor L-NG-nitro arginine (L-NOARG) antagonized the behavioral effects of a benzodiazepine (BZ) in a mouse paradigm for screening anxiolytic drug activity. Because other research has found that the anesthetic gas nitrous oxide (N2O) also produces BZ-like behavioral effects, the present research was conducted to ascertain whether NO might also be involved in N2O anxiolysis. Male Swiss-Webster mice were tested in an elevated plus-maze inside an inflatable glovebag. Exposure to N2O significantly increased exploratory activity on the open arms of the plus-maze, as measured by the number of entries into the open arms and the time spent on the open arms. Pretreatment with L-NOARG significantly reduced the N2O-induced elevation in open arm activity. This antagonism of the N2O effect was reversed by ICV treatment of L-NOARG-pretreated mice with L-arginine but not D-arginine. These findings indicate that NO possibly mediates behavioral effects of N2O in an animal model for anxiety.