Serotonergic modulation of photically induced increase in melatonin receptor density and Fos immunoreactivity in the suprachiasmatic nuclei of the rat.
The mammalian suprachiasmatic nuclei (SCN) contain a circadian clock which is regulated by neuronal photic and non-photic afferences. Among these, the serotonergic input originating from the dorsal raphe nucleus (DRN) is extremely important. In rats, a light pulse administered during the dark period is known to induce the expression of the immediate early gene c-fos and to increase melatonin receptor density in the SCN. The aim of this study was to assess whether, in rats, these two phenomena were regulated by serotonin, acting via 5-HT1A receptors. Three days after pinealectomy, 4 groups of rats were injected i.p. 90 min before sacrifice with respectively: (1) vehicle, (2) the 5-HT1A-agonist 8-OH-DPAT (5 mg/kg), (3) the 5-HT1A-antagonist NAN-190 (10 mg/kg) or (4) NAN-190 and the 8-OH-DPAT. Half of the animals from each group were exposed to light for 60 min before sacrifice and the other half remained in darkness. Sacrifice took place 5 to 6 h after lights off. Our results show that the antagonist NAN-190: (1) completely blocked the photically-induced increase of melatonin receptor density in the SCN, with an IC50 = 0.352 +/- 0.103 mg/kg, and (2) partially blocked (30%) the photic induction of Fos (the protein product of c-fos) in the ventrolateral subdivision of the SCN. The agonist 8-OH-DPAT enhanced the photically-induced increase of melatonin receptors by 10% and decreased the photically-induced increase in Fos by 18%. Both drugs were devoid of any effect in non-light exposed animals. From these results we may suggest that, in rats, there is a serotonergic control of the neuronal path driving photic information to the SCN. This regulation seems to occur through 5-HT1A or 5-HT1a-like receptors.
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Neurobiologie des Fonctions Rythmiques ed Saisonnières, URA-CNRS 1332, Université Louis Pasteur, Strasbourg, France.
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D008027:Light; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D044094:Receptors, Melatonin; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*
D010879:Piperazines; D016760:Proto-Oncogene Proteins c-fos; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin