Use of benzodiazepines to manipulate the circadian clock regulating behavioral and endocrine rhythms.

Extensive studies have now been carried out demonstrating that the systemic administration of the short-acting benzodiazepine, triazolam, can have pronounced effects on both behavioral and endocrine circadian rhythms. For example, three daily injections of triazolam can phase-advance the circadian rhythm of pituitary luteinizing hormone release and locomotor activity by about 2-3 h in female hamsters maintained in constant light. Triazolam has also been found to facilitate the rate of reentrainment of the activity rhythm following an 8-hour advance or delay in the light-dark cycle. Limited studies with other short-acting benzodiazepines indicate that the effects of triazolam on the circadian system of hamsters can be generalized to this class of drugs. Recent studies in humans indicate that treatment with triazolam can alter the time it takes for human endocrine rhythms to become reentrained following an 8-hour delay in the sleep-wake and light-dark cycle. Such findings raise the possibility that short-acting benzodiazepines may prove useful in reducing the symptoms associated with 'jet-lag' and rotating shift-work schedules as well as in the treatment of various physical and mental illnesses that have been associated with a disorder of biological timekeeping.