Low and high doses of benzodiazepine receptor inverse agonists respectively improve and impair performance in passive avoidance but do not affect habituation.

The benzodiazepine receptor inverse agonists, methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) and N-methyl-beta-carboline-3-carboxamide (FG 7142), were given to rats at various stages of a passive avoidance task. When the drugs were given before trial 1, low doses enhanced, and high doses impaired, performance as assessed 24 h later. A group given drugs on both trials showed that the impairment was not due to state-dependent effects. When the drugs were given immediately after trial 1, or before trial 2, they were without effect, except for the low dose of DMCM which impaired consolidation. It is discussed whether the changes in passive avoidance performance are due to direct or indirect effects. Between-trial habituation of exploratory head-dipping was measured in a holeboard. When FG 7142 was given before trial 1, the high dose impaired between-trial response decrement; but this was because it decreased the level of head-dipping on trial 1. When FG 7142 was given immediately after trial 1, or before trial 2, it was without effect on between-trial habituation.