Animal psychopharmacological models: Use of conflict behavior in predicting clinical effects of anxiolytics and their mechanism of action

Abstract

In the effort to identify and evaluate pharmacological agents therapeutically useful in anxiety, animal models with a high predictability of clinical efficacy is essential. It has been found that conflict behavior in rats and monkeys is useful in identifying pharmacological properties that are highly correlated with clinical antianxiety effects. Recent data will be presented to show that one can also measure the anticonflict activity of diazepam directly in humans, thus confirming and extending the relevance of such effects in animals. Once having established the correlation of such effects in animals with clinical antianxiety activity in patients, this model was useful in exploring possible mechanisms of action of anxiolytics. We have found a high correlation of the potency of benzodiazepine compounds which bind to the benzodiazepine receptor with their anticonflict effects. In addition, non-benzodiazepine agents which bind to this receptor also have anticonflict effects. Studies with methysergide and cinanserin in the anticonflict model lend support to the hypothesis that such antianxiety effects may be related to an interaction with the serotonergic system. Studies of the role of GABA in antianxiety activity will also be discussed. Anticonflict activity of diazepam is antagonized by the recently described specific benzodiazepine antagonist compound RO 15-1788.