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Changes in the Phase Response Curve of the Circadian Clock to a Phase-Shifting Stimulus

Centre des Rythmes Biologiques, School of Medicine, Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium, Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208

Fred W. Turek

Centre des Rythmes Biologiques, School of Medicine, Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium, Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208

Experiments were conducted in hamsters to determine whether the phase response curve (PRC) to injections of the short-acting benzodiazepine triazolam is a fixed or a labile property of the circadian clock. The results indicated that (1) both the shape and the amplitude of the PRC to triazolam generated on the first day of transfer from a light-dark cycle (LD 14:10) to constant darkness (DD) (i.e., PRC_LD) were different from those of the PRC generated after many days in DD (PRC_DD); and (2) the phase-shifting effects of triazolam on the activity rhythms of hamsters transferred from LD 14:10 or 12:12 to DD changed dramatically within the fist 8-9 days spent in DD. In an attempt to accelerate the resynchronization of the circadian clock of hamsters subjected to an 8-hr advance in the LD cycle, triazolam was given to the animals at a time selected on the basis of the characteristics of PRC_LD. The activity rhythms of five of eight triazolam-treated animals were resynchronized to the new LD cycle within 2-4 days after the shift, whereas those of most of the control animals were resynchronized 21-29 days after the shift. These findings suggest that attempts to use pharmacological or nonpharmacological tools to phase-shift circadian clocks under entrained conditions should take into account information derived from PRCs generated at the time of transition from entrained to free-running conditions.

Key Words: circadian • rhythm • clock • phase • period • benzodiazepines • triazolam • activity • arousal

Journal of Biological Rhythms, Vol. 7, No. 2, 137-147 (1992)
DOI: 10.1177/074873049200700205


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