An oral melatonin replacement regimen that re‐establishes the normal circadian levels of urinary 6‐sulphatoxymelatonin in functionally pinealectomized rats

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Abstract
Wistar rats maintained on a 12‐hr daily photoperiod (LD 12:12 cycle) exhibited a diurnal rhythm in urinary 6‐sulphatoxymelatonin (aMT6s) concentrations with peak levels in the scotophase. Light‐induced functional pinealectomy (FPX) abolished the nocturnal rise in aMT6s, lowering it to photophase levels. The objective of the study was to formulate an oral melatonin replacement regimen that would restore a normal rhythmic output of urinary aMT6s in functionally pinealectomised rats. Three regimens of sequential doses of melatonin were tested. Of these, the regimen with melatonin concentrations of 4 ng, 12 ng, 65 ng, and 4 ng per ml of drinking water given to rats during the 1st, 2nd, 3rd, and 4th 3‐hr periods, respectively, of the 12‐hr FPX phase, was found to generate a urinary aMT6s level that closely resembled the natural level and rhythm exhibited under an LD 12:12 cycle. This dose is considered appropriate to restore certain melatonin‐mediated physiological functions in Wistar rats subjected to FPX.