Melatonin administration: effects on rodent circadian rhythms

Previous research has demonstrated a lack of effect of pinealectomy upon the generation of rodent circadian activity rhythms and only a subtle effect upon their reentrainment after phase-shifts of the light-dark cycle. In contrast, our pharmacological studies on melatonin indicate that the pineal gland may be more important than hitherto believed. The main outcome of a preliminary pilot experiment on the effect of daily injections of melatonin, arginine vasotocin, melanocyte-stimulating hormone and a beta-blocker on rat free-running activity rhythms in constant darkness was that melatonin appeared to have entrainment properties. This was clearly demonstrated in a second experiment although entrainment did not occur until the onset of the activity rhythm coincided with the daily injection. In contrast, when melatonin was administered ad lib, in the drinking water to six rats housed in constant dim light, there was apparently a lengthening of the free-running period. The effects of 17 days of melatonin injections given at four different times of day to different groups of rats on re-entrainment of activity rhythms after a 5 h phase-advance of darkness were assessed. Results were confounded by the response of some control rats. However, after an 8 h advance of darkness and daily injection at the time of day of the previous dark onset, melatonin-injected rats phase-advanced, whereas vehicle-injected and uninjected control rats phase-delayed. Thus melatonin can alter the direction, but not necessarily the rate, of re-entrainment. The relevance of some of these findings with pharmacological doses of melatonin to the function of endogenous melatonin is discussed.