Suprachiasmatic control of melatonin synthesis in rats: inhibitory and stimulatory mechanisms

Jan 25, 2003The European journal of neuroscience

How the brain’s internal clock controls melatonin production in rats through activating and blocking signals

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Abstract

Ablation of the suprachiasmatic nucleus (SCN) completely eliminated the day/night difference in melatonin synthesis.

Bilateral lesions to the SCN, paraventricular nucleus (PVN), or removal of the superior cervical ganglion (SCG) impacted melatonin production.
In PVN-lesioned and ganglionectomised rats, melatonin synthesis was reduced to 12% of normal night-time levels.
SCN-lesioned rats exhibited melatonin levels at 30% of night-time control levels and showed constant secretion patterns.
All treatments disrupted the typical 24-hour rhythm of melatonin synthesis in the pineal gland.
The results suggest that the SCN provides both inhibitory and stimulatory inputs to the melatonin rhythm generating system.

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The suprachiasmatic nucleus (SCN) controls the circadian rhythm of melatonin synthesis in the mammalian pineal gland by a multisynaptic pathway including, successively, preautonomic neurons of the paraventricular nucleus (PVN), sympathetic preganglionic neurons in the spinal cord and noradrenergic neurons of the superior cervical ganglion (SCG). In order to clarify the role of each of these structures in the generation of the melatonin synthesis rhythm, we first investigated the day- and night-time capacity of the rat pineal gland to produce melatonin after bilateral SCN lesions, PVN lesions or SCG removal, by measurements of arylalkylamine N-acetyltransferase (AA-NAT) gene expression and pineal melatonin content. In addition, we followed the endogenous 48 h-pattern of melatonin secretion in SCN-lesioned vs. intact rats, by microdialysis in the pineal gland. Corticosterone content was measured in the same dialysates to assess the SCN lesions effectiveness. All treatments completely eliminated the day/night difference in melatonin synthesis. In PVN-lesioned and ganglionectomised rats, AA-NAT levels and pineal melatonin content were low (i.e. 12% of night-time control levels) for both day- and night-time periods. In SCN-lesioned rats, AA-NAT levels were intermediate (i.e. 30% of night-time control levels) and the 48-h secretion of melatonin presented constant levels not exceeding 20% of night-time control levels. The present results show that ablation of the SCN not only removes an inhibitory input but also a stimulatory input to the melatonin rhythm generating system. Combination of inhibitory and stimulatory SCN outputs could be of a great interest for the mechanism of adaptation to day-length (i.e. adaptation to seasons).

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Suprachiasmatic control of melatonin synthesis in rats: inhibitory and stimulatory mechanisms

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