Letter | Published:

A benzodiazepine used in the treatment of insomnia phase-shifts the mammalian circadian clock

Naturevolume 321pages167168 (1986) | Download Citation



Between 5 and 20% of the adult population in Western countries suffer from insufficient and/or unsatisfying sleep1,2, often associated with certain psychiatric disorders or with certain types of professional activities (for example, shift workers) and travel schedules (for example, jet lag)1,3,4. The benzodiazepines are at present the drug treatment of choice for the management of anxiety and stress-related conditions as well as insomnia5. Benzodiazepines are thought to act by potentiating the action of the neurotransmitter γ-aminobutyric acid (GABA), a widely distributed transmitter in the central nervous system6. The circadian system has a key role in the regulation of the sleep-wake cycle7–12, and at least some forms of insomnia may be the result of a disorder of the circadian sleep–wake rhythm8,9. Similarly, at least some forms of depression may also involve disruption of normal circadian rhythmicity13,14. A central pacemaker for the generation of many circadian rhythms in mammals, including the sleep–wake cycle, appears to be located in the suprachiasmatic nucleus15, and recent research indicates that both cell bodies and axons containing GABA are present within the bilaterally paired suprachiasmatic nuclei16,17. These findings raise the possibility that the benzodiazepines, commonly prescribed for sleep and mental disorders, may have an effect on the central circadian pacemaker. Here we report that the acute administration of triazolam, a short-acting benzodiazepine18 commonly prescribed for the treatment of insomnia, induces a phase-shift in the circadian rhythm of locomotor activity in golden hamsters. This suggests a role for GABA-containing neurones in the mammalian circadian system.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Akerstedt, T. Experientia 40, 417–422 (1984).

  2. 2

    Mellinger, G. D., Balter, M. B. & Uhlenhuth, E. H. Archs gen. Psychiat. 42, 225–232 (1985).

  3. 3

    Moore-Ede, M. C., Czeisler, C. A. & Richardson, G. S. New Engl. J. Med. 309, 530–536 (1983).

  4. 4

    Desir, D. et al. J. clin. Endocr. Metab. 52, 628–641 (1981).

  5. 5

    J. Am. med. Ass. 251, 2410–2414 (1984).

  6. 6

    Müller, W. E. in Neuroreceptors (ed. Hucho, F.) 3–13 (de Gruyter, Berlin, 1982).

  7. 7

    Aschoff, J. & Wever, R. Fedn Proc. 35, 2326–2332 (1976).

  8. 8

    Czeisler, C. A., Weitzman, E. D., Moore-Ede, M. C., Zimmerman, J. C. & Kronauer, R. E. Science 210, 1264–1267 (1980).

  9. 9

    Weitzman, E. D. et al. Archs gen. Psychiat. 38, 737–746 (1981).

  10. 10

    Winfree, A. T. Am. J. Physiol. 245, R497–R504 (1983).

  11. 11

    Daan, S., Beersma, D. G. M. & Borbely, A. A. Am. J. Physiol. 246, R161–R178 (1984).

  12. 12

    Folkard, S., Hume, K. I., Minors, D. S., Waterhouse, J. M. & Watson, F. L. Nature 313, 678–679 (1985).

  13. 13

    Linkowski, P. et al. J. clin. Endocr. Metab. 61, 429–438 (1985).

  14. 14

    Wehr, T. A. & Goodwin, F. K. (eds) Circadian Rhythms in Psychiatry (Boxwood, Pacific Grove, California, 1983).

  15. 15

    Turek, F. W. A. Rev. Physiol. 47, 49–64 (1985).

  16. 16

    Card, J. P. & Moore, R. Y. Neuroscience 13, 415–431 (1984).

  17. 17

    Van den Pol, A. N. & Tsujimoto, K. L. Neuroscience 15, 1049–1086 (1985).

  18. 18

    Eberts, F. S., Philopoulos, B. S., Reineke, B. S. & Vliek, R. W. Clin. Pharmac. Ther. 29, 81–93 (1981).

  19. 19

    Earnest, D. J. & Turek, F. W. Proc. natn. Acad. Sci. U.S.A. 82, 4277–4281 (1985).

  20. 20

    Ellis, G. B., McKlveen, R. E. & Turek, F. W. Am. J. Physiol. 242, R44–R50 (1982).

  21. 21

    Daan, S. & Pittendrigh, C. S. J. comp. Physiol. 106, 253–266 (1976).

  22. 22

    Ralph, M. R. & Menaker, M. Brain Res. 325, 362–365 (1985).

  23. 23

    Seidel, W. F., Roth, T., Roehrs, T., Zorick, F. & Dement, W. C. Science 224, 1262–1264 (1984).

  24. 24

    Walsh, J. K., Muehlbach, M. J. & Schweitzer, P. K. Sleep 7, 223–229 (1984).

  25. 25

    Van Cauter, E. & Turek, F. W. Perspectives Biol. Med. (in the press).

Download references

Author information


  1. Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois, 60201, USA

    • Fred W. Turek
    •  & Susan Losee-Olson


  1. Search for Fred W. Turek in:

  2. Search for Susan Losee-Olson in:

About this article

Publication history



Issue Date



Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.