Artificial induction of melatonin rhythms by programmed microinfusion

Melatonin was slowly and intermittently infused into rats via an apparatus that allowed it to be discharged from a subcutaneous implant according to a predetermined temporal program. We found that infusion of an aqueous solution of melatonin, mixed with a dye, or of an immiscible fluid lacking melatonin or dye, could be monitored by measuring levels of melatonin or of dye in the rats' urine. We observed a 24-hour rhythm in melatonin excretion which corresponded to the times of its infusion by the apparatus. Approximately 0.1% of infused melatonin was recovered unchanged in the urine. This method of administering exogenous melatonin may facilitate explaining the physiological significance of rhythms in its secretion and rhythms in plasma levels of other hormones.