ANTIDEPRESSANT PHARMACOLOGY OF THE RODENT CIRCADIAN SYSTEM

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One of the major features of affective illness is disruption of the circadian sleep-wake cycle characterized by loss of sleep, intermittent and early morning wakefulness. Accompanying this disturbance are abnormalities in the temporal relationship of physiological processes such as hormone release and temperature regulation with the sleep-wake cycle. One prediction of the phase advance hypothesis of affective illness is that re-establishment of more normal temporal phase relationships between disordered circadian rhythms may result in remission of depressed symptomotology. The mechanism of antidepressant chemical treatments may be consistent with this prediction; previous reports indicate the psychoactive medications lithium and the MAO inhibitor clorgyline affect the mammalian circadian system. We have therefore begun to evaluate antidepressant chemical effects on the rodent circadian system. This project has necessitated the design, construction, and evaluation of a rodent circadian rhythm monitoring facility. In addition, we have recently completed preliminary experiments designed to clarify clorgyline's precise effect on the rodent circadian system. Our studies to date demonstrate the rodent circadian facility is performing as designed; animals exhibit circadian patterns similar to those in controlled circadian laboratories elsewhere. Our pharmacological studies indicate a) direct or indirect clorgyline input to the hamster circadian pacemaker and b) clorgyline modification of the hamster rest-activity cycle. While this evidence is preliminary, we feel these data are currently the most compelling evidence of antidepressant chemical input to the rodent circadian pacemaker. Our current research plans are to replicate these findings and extend our observations to determine the mechanism and site(s) of clorgyline's input to the circadian system.