Entrainment of the Circadian Activity Rhythm to the Light-Dark Cycle Can Be Altered by a Short-Acting Benzodiazepine, Triazolam

The circadian rhythm of locomotor activity in hamsters maintained in either constant darkness or constant light can be phase-shifted by a single injection of the short-acting benzo diazepine, triazolam. These results suggest that treatment with triazolam may also alter the entrainment pattern of circadian rhythms in animals that are synchronized to a light-dark (LD) cycle. To test this hypothesis, hamsters maintained on an LD 6:18 light cycle received daily injections of triazolam (or vehicle) for 10-12 days, and any subsequent effects on the phase relationship between the onset of activity and the LD cycle were determined. Daily injections of triazolam (but not vehicle) induced pronounced advances or delays in the phase relationship between the entrained activity rhythm and the LD cycle; the direction of the shift was dependent on the time of the injection. Taken together with data from previous studies, these results suggest that triazolam, and perhaps other short-acting benzodiazepines, can be used to manip ulate the mammalian circadian clock under a variety of experimental conditions.