Antagonism of nitrous oxide-induced anxiolytic-like behavior in the mouse light/dark exploration procedure by pharmacologic disruption of endogenous nitric oxide function.

RATIONALE: Previous studies have shown the anxiolytic-like effects of nitrous oxide (N(2)O) to be sensitive to antagonism by non-specific inhibitors of nitric oxide synthase (NOS).
OBJECTIVES: The present study was conducted to demonstrate further the involvement of nitric oxide (NO) and ascertain whether a specific isoform of NOS is involved in N(2)O-induced behavior in mice.
METHODS: Male NIH Swiss mice were tested in the light/dark exploration test to determine how N(2)O-induced behavior was affected by the following pretreatments: the NO scavenger hemoglobin (Hb); the selective nNOS-inhibitor S-methyl- l-thiocitrulline (SMTC); the selective eNOS-inhibitor N(5)-(1-iminoethyl)- l-ornithine ( l-NIO); and the selective iNOS-inhibitor 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT). Furthermore, NOS activity was assessed in the whole brain as well as five brain areas of N(2)O- versus room air-exposed mice to determine the effects of N(2)O on NOS activity.
RESULTS: The behavioral effects of N(2)O in the light/dark exploration test were significantly attenuated following pretreatment with Hb (2.0 nmol, i.c.v.), SMTC (0.3 micro g and 1.0 micro g per mouse, i.c.v.) and the higher dose of l-NIO (30 mg/kg, s.c.). However, the N(2)O-induced behavioral effect was unaltered by pretreatment with either the lower dose of l-NIO (10 mg/kg, s.c.) or AMT (1.0 mg/kg and 3.0 mg/kg, s.c.). Finally exposure to 50% N(2)O for 15 min significantly increased NOS activity in the cerebellum and corpus striatum but not in other brain regions or whole brain.
CONCLUSION: These findings provide further support for the hypothesis that NO is involved in N(2)O-induced anxiolytic-like behavior and that this NO is the product of nNOS enzyme activity.