Effects of benzodiazepine receptor antagonist, flumazenil, on antinociceptive and behavioural responses to the elevated plus-maze in mice.

Brief exposure to an elevated plus-maze has been shown to induce antinociception in male mice, a reaction that is not attenuated by manipulations of opiate receptors but which is fully blocked by diazepam. The present study examined the effects of the benzodiazepine receptor antagonist, flumazenil (5-20 mg/kg), on behavioural and antinociceptive responses to the elevated plus-maze in male DBA/2 mice. The results showed that, in the absence of an effect on total arm entries or rearing, flumazenil increased the time spent on the closed arms of the maze (an anxiogenic profile) and significantly enhanced antinociception induced by the elevated plus-maze. Data are discussed in relation to an "endogenous ligand theory" and it is concluded that the present findings are consistent with the proposed involvement of anxiety in at least certain forms of adaptive inhibition of pain.