A melatonin agonist and N-acetyl-N2-formyl-5-methoxykynurenamine accelerate the reentrainment of the melatonin rhythm following a phase advance of the light-dark cycle

The rate of entrainment of the urinary 6-sulphatoxymelatonin rhythm to a phase-advanced photoperiod and the influence of a melatonin agonist and melatonin analogues and metabolites on the entrainment were investigated in male rats. Following an 8-h advance of a 14:10 light-dark photoperiod, the 6-sulphatoxymelatonin rhythm was disrupted completely for two days and became entrained after 5-6 days. Subcutaneous injection of the melatonin agonist, 6-chloromelatonin (0.5 mg/kg) and the brain metabolite, N-acetyl-N2-formyl-5-methoxykynurenamine (aFoMK, 10 mg/kg) two hours after dark onset on the day after the phase advance accelerated the entrainment to the new photoperiod. N-acetyl-5-methoxykynurenamine, 6-chloro-2,3-dihydromelatonin, 1,3-dihydro-5-(ethylacetamide)-7-methoxy-2H-1,4-benzodiazepin++ +-2-one and N-formylkynurenine were all without effect at a dose of 10 mg/kg. Treatment of rats with aFoMK on the day of the phase advance (day 0) together with treatment on day +1 accelerated the entrainment to the photoperiod whereas a single injection on day +2 or injections on day +1 and day +2 were without effect at a dose of 10 mg/kg. These results: (a) demonstrate the usefulness of monitoring urinary 6-sulphatoxymelatonin rhythms for pineal studies; (b) show that melatonin can indirectly influence its own secretion, presumably by interactions with the suprachiasmatic nucleus; and (c) provide further evidence for the biological activity of the brain metabolite of melatonin, N-acetyl-N2-formyl-5-methoxykynurenamine.