This project investigates the effect of antidepressant drugs on the light sensitivity of the circadian clock. The circadian clock helps to regulate the daily pattern of human behavior. Exposure to light resets the timing of the clock and the pattern of behaviors controlled by the clock. Drugs that alter the responsiveness of the clock to light reset the temporal relationship that exists between the environment and endogenous physiological processes. In many mammals, the circadian clock consists of two oscillators that control morning and evening activity. These oscillators exhibit different properties in their response to light. For example, morning light advances the timing of the circadian pacemaker by phase-shifting the morning oscillator. Evening light delays the timing of the circadian pacemaker by phase-shifting the evening oscillator. Our data suggests that chronic treatment with the antidepressant drug clorgyline differentially affects light sensitivity to morning and evening light. This change in sensitivity contributes to the establishment of new stable phase relationships between the circadian pacemaker and the environment. However, due to their different sensitivities to light, high intensity light pulses may drive endogenous components of the circadian system into unstable phase relationships with respect to the body temperature rhythm. These effects may be related to the antidepressant mechanisms of these drugs, or to the disorganized sleep-wake cycle sometimes observed in humans.
