Interactions of three benzodiazepine receptor inverse agonists with ethanol in a plus-maze test of anxiety.

The effects of RO 15-4513, RO 15-3505 and FG 7142 on the anxiolytic properties of ethanol in mice were investigated using the plus-maze test of anxiety. Before being tested on the plus-maze, the mice were tested in a holeboard apparatus. All three inverse agonists attenuated the reduction in exploration caused by ethanol in the holeboard test. In the plus-maze, only RO 15-4513 and FG 7142, which possess anxiogenic properties when administered alone, attenuated ethanol's anxiolytic effect. RO 15-3505, which alone had no effect on anxiety, failed to significantly reduce ethanol's anxiolytic effect. Neither RO 15-4513 nor FG 7142 reduced the increase in the total number of arm entries caused by ethanol. These data indicate that the interaction between ethanol and benzodiazepine receptor ligands depends both on the intrinsic properties of the ligands and the behavior under investigation.