Activity of some benzodiazepine receptor ligands with reduced sedative and muscle relaxant properties on stress-induced electrocorticogram arousal in sleeping rats.

Arousal of the electrocorticogram induced by intermittent footshocks in sleeping rats was originally developed to detect hypnotic compounds. A modified shortened protocol is described in which a 2.5-hr nonstressed control period is followed by drug or vehicle administration and a further 5.5-hr recording of the electrocorticogram in the presence of intermittent footshock. The arousal induced by the footshock is reversed by the benzodiazepine chlordiazepoxide and by agents that displace brain benzodiazepine binding but that do not possess the muscle relaxant and sedative properties of benzodiazepines (CL218872, premazepam, ZK91296, RU 43028, and CGS9896). Nonstressed arousal during normal waking was reduced to only a small extent by chlordiazepoxide or any of the other agents tested, suggesting that the footshock-induced arousal is sensitive to the anxiolytic properties of such agents.