Involvement of cyclic GMP-dependent protein kinase in nitrous oxide-induced anxiolytic-like behavior in the mouse light/dark exploration test

The second messenger cyclic GMP (cGMP) plays a role in the anxiolytic-like behavioral response of mice to nitrous oxide (N2O). This study was conducted to determine whether this behavioral effect of N2O is affected by inhibition of cGMP-dependent protein kinase (PKG). N2O-induced behavior in the light/dark exploration test was significantly attenuated by the PKG inhibitors H-8 and Rp-8-pCPT-cGMPS but not Rp-8-pCPT-cAMPS, an inhibitor of cAMP-dependent protein kinase. These findings implicate PKG in the mediation or modulation of the anxiolytic-like behavioral response to N2O.