title: In vivo evidence for a controlled offset of melatonin synthesis at dawn by the suprachiasmatic nucleus in the rat.
abstract: The daily rhythm of melatonin synthesis in the rat pineal gland is controlled by the central biological clock, located in the suprachiasmatic nucleus (SCN), via a multi-synaptic pathway involving, successively, neurones of the paraventricular nucleus of the hypothalamus (PVN), sympathetic preganglionic neurones of the intermediolateral cell column of the spinal cord, and norepinephrine containing sympathetic neurones of the superior cervical ganglion. Recently, we showed that, in the rat, the SCN uses a combination of daytime inhibitory and nighttime stimulatory signals toward the PVN-pineal pathway in order to control the daily rhythm of melatonin synthesis, GABA being responsible for the daytime inhibitory message and glutamate for the nighttime stimulation. The present study was initiated to further check this concept, and to investigate the involvement of the inhibitory SCN output in the early morning circadian decline of melatonin release, with the hypothesis that, at dawn, the increased release of GABA onto pre-autonomic PVN neurones results in a diminished norepinephrine stimulation of the pineal, and ultimately an arrest of melatonin release. First, we established that prolonged norepinephrine stimulation of the pineal gland was indeed sufficient to prevent the early morning decline of melatonin release. Blockade of GABA-ergic signaling in the PVN at dawn could not prevent the early morning decline of melatonin completely. Therefore, these results show that an increased GABAergic inhibition of the PVN neurones that control the sympathetic innervation of the pineal gland, at dawn, is not sufficient to explain the early morning decline of melatonin release.
authors.affiliation: Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam, The Netherlands. s.perreau@nih.knaw.nl
authors.forename: S
authors.initials: S
authors.lastname: Perreau-Lenz
authors.forename: A
authors.initials: A
authors.lastname: Kalsbeek
authors.forename: J
authors.initials: J
authors.lastname: Van Der Vliet
authors.forename: P
authors.initials: P
authors.lastname: Pévet
authors.forename: R M
authors.initials: RM
authors.lastname: Buijs
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002940:Circadian Rhythm / Q000502:physiology*; D003624:Darkness; D018756:GABA Antagonists / Q000494:pharmacology; D008027:Light; D008297:Male; D008550:Melatonin / Q000096:biosynthesis*; D017551:Microdialysis; D009638:Norepinephrine / Q000494:pharmacology; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D013268:Stimulation, Chemical; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000502:physiology*
chemical_list: D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D018756:GABA Antagonists; D008550:Melatonin; D009638:Norepinephrine; D001640:Bicuculline