Interaction between nitrous oxide and diazepam in the mouse staircase test

The interaction between nitrous oxide and diazepam was assessed in the mouse staircase test. In this paradigm, the numbers of rears (NR) (simultaneous standing on hindlegs and sniffing the air) and steps ascended (NSA) reflect anxiety and locomotor activity, respectively. Antianxiety drugs characteristically reduce NR but not NSA, while sedative drugs reduce both NR and NSA in generally parallel fashion. In this study, increasing concentrations of nitrous oxide alone produced progressively greater and statistically significant increases in NSA. Nitrous oxide alone had no significant effect on NR until, at a concentration of 75%, it decreased NR. Diazepam alone decreased NR equally and significantly at all doses. With certain combinations of concentration and dose, nitrous oxide enhanced the effect of diazepam on NR without altering NSA. These findings suggest that nitrous oxide can increase the antianxiety effect of diazepam without increasing its sedative effect in the mouse staircase paradigm.