Altering the mammalian circadian clock with the short-acting benzodiazepine, triazolam

The systemic administration of triazolam alters circadian rhythms of hamsters under both entrained (synchronized to a circadian period) and free-running (in the absence of a synchronizing light-dark cycle) conditions. In the latter conditions (i.e. during exposure to constant light or darkness), single injections of triazolam can induce a permanent phase-shift in both behavioral and endocrine rhythms. Repeated injections at fixed circadian intervals can entrain the rhythm of locomotor activity, and in the presence of a synchronizing light-dark cycle, daily injections of triazolam can alter the phase relationship of the activity rhythm to the light-dark cycle. Moreover, following a shift in the light-dark cycle, a single injection of triazolam can shorten the time it takes for the activity rhythm to be resynchronized to the new lighting schedule. In addition to implicating a role for the neurotransmitter GABA in the circadian organization of mammals, these findings may have important clinical implications. If short-acting benzodiazepines can have similar effects on the human circadian clock, they could 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 in biological timekeeping.