Journal of Comparative Physiology A

, Volume 164, Issue 6, pp 805–814 | Cite as

Central administration of muscimol phase-shifts the mammalian circadian clock

  • Richard D. Smith
  • Shin -Ichi T. Inouye
  • Fred W. Turek


The suprachiasmatic nucleus (SCN) of the hypothalamus contains a neural oscillatory system which regulates many circadian rhythms in mammals. Immunohistochemical evidence indicates that a relatively high density of GABAergic neurons exist in the suprachiasmatic region. Since intraperitoneal injections of the benzodiazepine, triazolam, have been shown to induce phase shifts in the free-running circadian rhythm of locomotor activity in the golden hamster, the extent to which microinjections of muscimol, a specific agonist for gamma-aminobutyric acid (GABA), may cause phase-shifts in hamster activity rhythms was investigated. Stereotaxically implanted guide cannulae aimed at the region of the SCN were used to deliver repeated microinjections in individual animals. A phase-response curve (PRC) generated from microinjections of muscimol revealed that the magnitude and direction of permanent phase-shifts in the activity rhythm were associated with the time of administration. The PRC generated for muscimol was characterized by maximal phase-advances induced 6 h before activity onset and by maximal phase-delays which occurred 6 h after activity onset. The PRC for muscimol had a shape similar to a PRC previously generated for the short-acting benzodiazepine, triazolam. Single microinjections of different doses of muscimol given 6 h before activity onset induced phase-advances in a dose-dependent fashion. Histological analysis revealed that phase shifts induced by the administration of muscimol were associated with the proximity of the injection site to the SCN area. These data indicate that a GABAergic system may exist within the suprachiasmatic region as part of a central biological clock responsible for the regulation of the circadian rhythm of locomotor activity in the golden hamster.


Locomotor Activity Circadian Rhythm Circadian Clock Triazolam Activity Rhythm 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



circadian time


gamma-aminobutyric acid


optic chiasm


phase-response curve


standard error of mean


suprachiasmatic nuclei




third ventricle


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Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • Richard D. Smith
    • 1
  • Shin -Ichi T. Inouye
    • 2
  • Fred W. Turek
    • 1
  1. 1.Department of Neurobiology and PhysiologyNorthwestern UniversityEvanstonUSA
  2. 2.Mitsubishi-Kasei Institute of Life SciencesTokyoJapan

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