Role of cyclic GMP in nitrous-oxide-induced anxiolytic-like behavior in the mouse light-dark exploration test

Nitric oxide (NO) has been implicated in the anxiolytic-like behavioral effects of nitrous oxide (N2O). This study was conducted to determine whether NO activates a soluble guanylyl cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway in the behavioral response to N2O in the light-dark exploration test. In mice pretreated with an sGC inhibitor, the increased light-compartment activity normally induced by N2O was significantly attenuated. Pretreatment with a cGMP phosphodiesterase inhibitor antagonized the anxiogenic effect of 15% N2O and enhanced the anxiolytic effect of 25% N2O, implying that cGMP reduces anxiety. These preliminary findings suggest that a signaling pathway involving NO and cGMP may mediate the behavioral effects of N2O.