Behavioral analysis of the effects and mechanisms of action of benzodiazepines.

Conflict behavior is a powerful tool to reveal relevant pharmacologic correlates of the therapeutically desirable properties of benzodiazepine antianxiety compounds. The predictability of its clinical effectiveness in psychoneuroses is very high, and important quantitative and qualitative differences between compounds in this chemical class can be shown using such a behavioral technique. It is important to take these differences into account when studying biochemical correlates or mechanisms of action within the benzodiazepine class. Conflict behavior has been used to evaluate several biochemical hypotheses concerning the mechanism of action for the antianxiety properties of benzodiazepines. These studies found that inhibition of cyclic AMP phosphodiesterase did not seem to be a relevant factor. Similarly, experiments with AOAA did not provide evidence to support the involvement of GABA with benzodiazepines' antianxiety properties, nor did glycine receptor affinities correlate significantly with anticonflict effects. Thus, while it is reasonable at present to associate either GABA or glycine with the muscle-relaxant or anticonvulsant properties of benzodiazepines, no support was provided in the conflict procedure for their involvement in the anxiolytic effects. Partial support was provided for the proposal that serotonin is involved in the benzodiazepines' anxiolytic activity. This was determined in studies with the serotonin antagonists cinanserin and methysergide, which had anti-conflict activity, as well as in studies of monoamine turnover after initial chlordiazepoxide treatments to previously undrugged, conflict-trained rats.