Phase shifts in the circadian activity rhythm induced by triazolam are not mediated by the eyes or the pineal gland in the hamster.

A single injection of the benzodiazepine triazolam, which is though to act by potentiating the effects of the neurotransmitter gamma-aminobutyric acid (GABA), can induce permanent phase shifts in the circadian rhythm of locomotor activity of hamsters. Occurrence of GABA immunoreactivity and benzodiazepine receptors in the retina, which contains photoreceptors that relay synchronizing light-dark information to the mammalian circadian system, raises the possibility that triazolam may influence circadian rhythmicity via an action on the retina. However, the phase shifting effects of triazolam on the activity rhythm were unaffected by blinding: the direction and the magnitude of the phase shifts were similar in blind hamsters and in sighted hamsters maintained in constant darkness. Furthermore, no change in response to triazolam was observed in hamsters studied through 84 days after blinding. In addition, benzodiazepine binding sites have been found in the mammalian pineal gland, which has also been implicated in circadian rhythmicity. Therefore, its possible involvement in mediating the phase advancing effects of triazolam on the circadian clock has also been tested: the response was similar in blind and blind-pinealectomized animals. These results indicate that the effects of triazolam on the circadian clock are not mediated by the eyes or the pineal gland.