Manipulation of the circadian clock with benzodiazepines: implications for altering the sleep-wake cycle.

Abnormal circadian rhythms have been linked to at least some forms of depression and to disturbances in the sleep-wake cycle. In addition, mental and physical disorders associated with rapid travel across time zones (i.e. the jet-lag syndrome) and with rotating shift-work schedules, are thought to involve a disruption of normal circadian rhythmicity. It might be possible to alleviate some of the adverse effects associated with abnormal circadian rhythms if pharmacological agents could be used to manipulate the central circadian pacemaker(s) that regulates these rhythms. Recent findings indicate that treatment with a short-acting benzodiazepine, triazolam, can induce major shifts in the circadian clock of golden hamsters. In the absence of a synchronizing light-dark cycle (i.e. during exposure to constant light or constant dark), a single injection of triazolam can induce a permanent phase shift in the circadian rhythm in locomotor activity. In addition, following a shift in the light-dark cycle, a single injection of triazolam can facilitate the time it takes for the activity rhythm to be resynchronized to the new lighting schedule. Triazolam, or drugs with similar phase-shifting effects on the mammalian circadian system, might be useful in the treatment of various sleep and mental disorders that have been associated with a disorder in circadian time-keeping in humans.