THE USE OF THE RAT ELEVATED PLUS-MAZE TO DISCRIMINATE BETWEEN NONSELECTIVE AND BZ-1 (OMEGA(1)) SELECTIVE, BENZODIAZEPINE RECEPTOR LIGANDS

The behavioral effects of a wide range of BZ (omega) receptor ligands, including non-selective full (alprazolam, clorazepate, chlordiazepoxi de and diazepam) and partial (bretazenil, imidazenil and Ro 19-8022) a gonists, and selective BZ-1 (omega(1)) (abecarnil, CL 218,872, CL 284, 846 and zolpidem) receptor ligands, were compared in the rat elevated plus-maze test. Behaviors recorded comprised the traditional indices o f anxiety as well as a number of ethologically derived measures. In ad dition, the specificity of drug effects was evaluated by measuring spo ntaneous locomotor activity in activity cages in separate groups of an imals. Results showed that all compounds tested not only increased the proportion of time spent and proportion of entries into the open arms of the maze (considered as traditional indices of anxiety) but also a ffected head-dippings and attempts at entry into open arms, which can be considered as indices of risk assessment responses. However the mag nitude of these effects was generally smaller with the BZ-1 (omega(1)) selective agents. Moreover, additional differences were apparent on t he total number of arm entries measure, which was significantly increa sed by most full and all partial agonists, but was unaffected by the s elective BZ-1 (omega(1)) compounds. If it is assumed that total arm en tries are contaminated by anxiety, the latter finding indicates a weak er anxiety-reducing potential of selective BZ-1 (omega(1)) ligands. Im portantly, the increase in total arm entries induced by the non-select ive agents was not associated with a similar effect on locomotion as r evealed in the actimeter. Finally, anxiolysis produced by the BZ-1 (om ega(1)) ligands was invariably observed at doses which reduced locomot or activity, suggesting that the anxiolytic-like effects of these comp ounds are confounded by decreases in locomotor activity.