Benzodiazepine blockade of passive-avoidance task in mice: a state-dependent phenomenon.

Four benzodiazepines (diazepam, chlordiazepoxide, halazepam, lorazepam) were tested for their effects on the acquisition of a passive-avoidance task in mice. This was done to determine whether amnesic effects, as reported in humans after diazepam and lorazepam, could be demonstrated by blockade of passive-avoidance responding in mice and, if so, to investigate the possible causes of the blockade by studying the relationships between the blockade and times of drug administration. Each of these benzodiazepines, at doses that did not alter overt behavior, blocked acquisition of the passive-avoidance response when they were administered to mice prior to the training session, but not when they were administered after the training session or prior to testing 24 h later. The block of avoidance responding was reversed, however, when the drugs were administered prior to both training and test sessions. These results suggest that state-dependent learning occurred; i.e., apparent amnesia occurred in the test session with untreated mice that had undergone passive-avoidance learning 24 h earlier under the influence of drug.