An ethological analysis of the effects of chlordiazepoxide and bretazenil (Ro 16-6028) in the murine elevated plus-maze.

The effects of chlordiazepoxide (2.5-15.0mg/kg), a full benzodiazepine receptor agonist, and bretazenil (5.0-30.0mg/kg), a partial benzodiazepine receptor agonist, were examined in the murine elevated plus-maze paradigm. Behaviours recorded comprised the traditional indices of anxiety as well as a number of ethologically derived measures. Results show that chlordiazepoxide (10-15mg/kg) and bretazenil (5-30mg/kg) not only decreased traditional indices of anxiety but also reduced risk assessment behaviours such as head-dipping and stretch attend postures from secure areas of the maze. Both compounds produced these effects without adversely affecting general activity levels. While traditional indices of anxiety did not clearly discriminate between the two compounds, some differences were apparent on the ethological measures. The dose-response curves for bretazenil were generally shallower than those for chlordiazepoxide, confirming its partial agonist profile. Together, these data support the view that benzodiazepine receptor partial agonists may have utility in the management of human anxiety disorders.