Daily Melatonin Treatments Regulate the Circadian Melatonin Rhythm in the Adult Djungarian Hamster

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Abstract
The present study tested the hypothesis that daily melatonin treatments influence the biological clock mechanism controlling the circadian melatonin rhythm. Adult male and female Djungarian hamsters in light:dark = 16L:8D (lights on 0300-1900 h) were administered melatonin subcutaneously (s.c.) each day (5 μg/0.2 ml saline) in the morning at 1000 h (AM) or late afternoon at 1700 h (PM); controls received a vehicle injection (CON). After 14 days, pineal and serum melatonin concentrations were determined at various times on the last day of treatment and the next day in constant darkness (no treatment). The rhythm in pineal gland melatonin content was similar in each of the three groups on the last day of treatment (about 6 h duration). On the next day in constant dark, the rising phase was advanced and duration extended by 2 h or more in melatonin-treated hamsters compared to that in CONs (ANOVA). In circulation, the melatonin rhythm in AM and PM groups was phase advanced (onset and peak) on both days of the study. Thus duration was extended by up to 4.5 h compared to that in saline-treated controls. Moreover, amplitude of the nighttime serum melatonin rise was elevated up to fivefold relative to that in the CON group (ANOVA and Accumulated Sums analysis). The effects of repeated melatonin treatments on amplitude and phase of the serum melatonin rhythm raise the possibility that the circadian clock that controls pineal gland production of melatonin may also regulate melatonin secretion. From this and another study, the apparent half-life of melatonin in circulation was estimated to be 7.5 min; the melatonin injection initially produced pharmacological concentrations that were followed by low serum melatonin levels within 2 h. Thus, in both melatonin treatment groups, the data suggest that two distinct periods of elevated serum melatonin were present each day The cellular mechanism for melatonin action must take into consideration how a brief interruption in elevated melatonin in circulation (about 1 h in the PM group) is recognized as a continuous duration (short daylength), whereas a more extended baseline period is transduced as an abbreviated or long daylength (about 7 h in the AM group). These data further suggest that the biological clock mechanism that generates the circadian melatonin rhythm is responsive to the influence of daily melatonin treatments and presumably to the feedback action of endogenous melatonin on its own rhythm in the Djungarian hamster in long days.

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