Influence of the mode of daily melatonin administration on entrainment of rat circadian rhythms.

In previous entrainment studies, melatonin (MEL) was administered by handling the animal, but because such handling may act as a confounding variable, the results from these studies are equivocal. The authors used MEL administration techniques that do not involve direct handling of the animal. Long Evans rats were used, and core body temperature (CBT) and wheel-running activity were recorded. One group of rats received a daily 1-h time-fixed infusion of MEL or the vehicle via a subcutaneous catheter. Animals in a second group had timed access to drinking water involving daily presence of drinking water containing MEL or the vehicle for 2 h at a fixed time of the day. Following entrainment to LD 12:12, both groups were transferred to constant darkness to free-run under vehicle administration. MEL was then administered, and entrainment occurred when activity onset coincided with MEL onset. Under both regimens, entrainment of wheel-running and CBT rhythms showed equal phase-relation to the onset of MEL administration, and free-running reoccurred when MEL was withdrawn. The authors concluded that MEL administration via drinking water and via infusion represent efficient ways to synchronize free-running rhythms in rats.