Stimulated activity mediates phase shifts in the hamster circadian clock induced by dark pulses or benzodiazepines

Abstract

A NUMBER of environmental and pharmacological stimuli capable of inducing phase shifts and/or period changes in the circadian clock of mammals have now been identified^1–3. Agents that can alter circadian clocks provide a means for investigating the cellular and neural mechanisms responsible for their generation, regulation and entrainment. Two stimuli that have been used to probe the basis of circadian rhythmicity are pulses of darkness on a background of constant light^4–8and injections of short-acting benzodiazepines, such as triazolam^9–11. Surprisingly, these two very different stimuli have remarkably similar phase-shifting effects on the circadian clock of hamsters. The observation that a short-term increase in locomotor activity occurs when the circadian activity rhythm of hamsters is shifted by dark pulses or triazolam injections^5,6,9, coupled with the finding that activity bouts themselves are capable of shifting this rhythm^12,13, raises the possibility that dark pulses or triazolam alter the circadian clock by inducing acute hyperactivity. Here we demonstrate that the phase-advancing and phase-delaying effects of dark pulses or triazolam on the circadian activity rhythm can be totally suppressed by immobilization of the animals during treatment. These results indicate that behavioural events mediate the phase-shifting effects of both dark pulses and triazolam on the circadian activity rhythm and question present hypotheses regarding the pathways by which light-dark information and pharmacological agents influence circadian pacemakers.