Acute tolerance to diazepam induced by benzodiazepines.

It was observed that the effectiveness of diazepam in causing sleep, as defined by the loss of righting reflex, was significantly decreased after a single exposure to either diazepam or lorazepam. RO 15-1788, a benzodiazepine antagonist, in contrast did not induce tolerance to diazepam. The mechanism for this acute tolerance is unclear. The rapidity in its development may exclude metabolic tolerance while alterations in brain sensitivity to diazepam remain a possibility.