Animal model studies of benzodiazepine-induced amnesia.

The development of a mouse passive avoidance test as a model for amnesia produced by benzodiazepines is described. The model appropriately classifies the amnesic potential of a wide range of psychoactive drugs as validated by clinical findings. Control experiments indicate that the effect is best described as anterograde amnesia resulting from a failure of consolidation. gamma-Aminobutyric acid (GABA) antagonists had almost no effect on benzodiazepine-induced amnesia, whereas the benzodiazepine-receptor antagonist Ro 15-1788 completely and specifically reversed it. This clinically confirmed finding suggests that benzodiazepine-induced amnesia is mediated through the benzodiazepine-receptor. However, in vivo inhibition of benzodiazepine binding does not correlate well with amnesia in the mouse, and some benzodiazepine-receptor agonists with potent CNS effects in other in vitro models do not produce amnesia. Additional work is needed to clarify what aspects of benzodiazepine receptor occupancy mediate amnesia.