Combined effects on the circadian clock of agents with different phase response curves: phase-shifting effects of triazolam and light.
Although light provides the primary signal for the entrainment of circadian pacemakers, a number of endogenous substances and pharmacological agents are also capable of resetting circadian pacemakers. Very little is known about the combined effects of photic and nonphotic agents on clock functions. We conducted a "double-pulse" experiment, in which two discrete stimuli are presented at different times within a single circadian cycle, to determine the combined effects of a 1-hr light pulse and injections of a benzodiazepine, triazolam, on the circadian rhythm of activity in the golden hamster. Our results suggest that, first, when given together as done in these experiments, the effects of triazolam and light are partially but not completely additive. Triazolam-induced phase advances appeared to make the effects of subsequent 1-hr light pulses more negative; phase delays were increased, and phase advances were decreased. Second, it appears that triazolam and light may alter the circadian pacemaker in very different ways, beyond the obvious difference in the shape of their phase response curves. The phase-shifting mechanics of the circadian system of the golden hamster appear to involve a longer response time to triazolam than to light pulses. Alternative possibilities to account for this difference are discussed.
Joy
J E
JE
Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208.
Turek
F W
FW
D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D006224:Cricetinae; D008027:Light; D008297:Male; D008647:Mesocricetus; D009043:Motor Activity / Q000502:physiology; D010775:Photic Stimulation; D014229:Triazolam / Q000494:pharmacology*
D014229:Triazolam