title: In the rat, exogenous melatonin increases the amplitude of pineal melatonin secretion by a direct action on the circadian clock.
abstract: The effect of exogenous melatonin on pineal melatonin synthesis was studied in the rat in vivo. Daily melatonin profiles were measured by transpineal microdialysis over 4 consecutive days in rats maintained on a 12-h light : 12-h dark schedule (LD 12 : 12). Curve-fitting was used to determine the amplitude of the peak of melatonin production, and the times of its onset (IT50) and offset (DT50). A subcutaneous injection of melatonin (1 mg/kg) at the onset of darkness (ZT12) induced an advance of IT50 on the second day after the treatment, in 50% of the animals kept in LD. When the animals were switched to constant darkness, the treatment caused no detectable advance of IT50, while 70% of individuals showed a significant delay in DT50 2 days after the injection. Locally infusing the drug by reverse microdialysis into the suprachiasmatic nuclei (SCN) failed to enhance the shift in melatonin onset. Following subcutaneous melatonin injection, a significant increase ( approximately 100%) in melatonin peak amplitude was observed. This increase persisted over 2 days and occurred only when the melatonin was applied at ZT12, but not at ZT6, 17 or 22. The effect was also observed when the drug was infused directly into the SCN, but not into the pineal. Thus, the SCN are the target site for the effect of exogenous melatonin on the amplitude of the endogenous melatonin rhythm, with a similar window of sensitivity as its phase-shifting effect on the pacemaker.
authors.affiliation: Laboratoire de Neurobiologie des Rythmes, UMR 7518 CNRS/Université Louis Pasteur, Strasbourg, France. bothorel@neurochem.u-strasbg.fr
authors.forename: Béatrice
authors.initials: B
authors.lastname: Bothorel
authors.forename: Stéphane
authors.initials: S
authors.lastname: Barassin
authors.forename: Michel
authors.initials: M
authors.lastname: Saboureau
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Perreau
authors.forename: Berthe
authors.initials: B
authors.lastname: Vivien-Roels
authors.forename: André
authors.initials: A
authors.lastname: Malan
authors.forename: Paul
authors.initials: P
authors.lastname: Pévet
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology*; D003624:Darkness; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D008297:Male; D008550:Melatonin / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology*; D017551:Microdialysis; D010775:Photic Stimulation; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000502:physiology
chemical_list: D008550:Melatonin