Decreased Sensitivity to Light of the Photic Entrainment Pathway during Chronic Clorgyline and Lithium Treatments

Abstract

Certain antidepressant drugs (ADs) cause disturbances in sleep that could result from their capacity to alter the timing of circadian rhythms. Effects on the timing of rhythms could be due to the drugs' known capacity to alter the frequency of the intrinsic rhythm of the circadian pacemaker, or to a capacity to modify the pacemaker's response to external stimuli that serve as time cues (Zeitgebers) that regulate the timing (phase) of its rhythm. To examine the possibility that ADs alter the sensitivity of the system that mediates the phaseshifting effects of light, hamsters were treated chronically with the MAOI, clorgyline, and lithium. Each hamster was then exposed to a single 5-min light pulse (intensity range = 0.00137 to 137 μW/cm2) at circadian phases known to elicit phase advances (CT18) and phase delays (CT13.5) in the daily onset of wheel running. The half-saturation constant ([.sigma]), photic sensitivity (1/[.sigma]), and maximum phase-shifting response to light were estimated from the best-fit stimulus response curves. In addition, threshold sensitivity, the light intensity required to produce a threshold phase-shifting response, was determined. Clorgyline decreased the magnitude of light-induced phase advances at each of the light intensities tested. Clorgyline also decreased the magnitude of light-induced phase delays at low light intensities, but increased the magnitude of phase delays at higher light intensities. Clorgyline decreased the sensitivity of the photic phase-shifting system, as indicated both by the threshold sensitivities at CT13.5 and CT18 and by 1/[.sigma] at CT13.5. Lithium decreased the threshold sensitivity at CT18, and 1/[.sigma] at CT13.5. Lithium decreased the magnitude of phase delays, but not phase advances. Clorgyline's effects on the photic entrainment pathway may be mediated by its effects on serotonin, which has been shown to modulate the pacemaker's response to morning and evening light, and by tolerance to this effect of serotonin. The fact that both clorgyline and lithium decrease the photic sensitivity of the entrainment pathway suggests that other psychoactive drugs might also share this property. It is possible that the decreased sensitivity to light of the entrainment pathway affects the clinical response to these and other psychoactive medications.