Increase of “antianxiety” activity and tolerance of behavioral depression during chronic administration of oxazepam

Summary

Oxazepam has two opposing actions on behavior: a responsedecreasing or depressant action and a response-increasing or disinhibitory action. The course of the two actions in chronic dosing was determined in rats in a test in which punished and unpunished schedules of reinforcement were alternated. The depressant action (measured by a decrease in the rate of unpunished behavior) was observed to undergo tolerance after 3–4 doses, while the disinhibitory action (measured by an increase in the rate of punished behavior) failed to show tolerance and even increased throughout the chronic series. The selective tolerance of the depressant action is probably due to neuronal adaptation, but changes in metabolism also may be involved. The increase in the rate of punished behavior is attributed, at least in part, to a progressive unmasking of the disinhibitory action as tolerance to the depressive action develops.