New light on the serotonergic paradox in the rat circadian system.
The main mammalian circadian clock, localized in the suprachiasmatic nuclei can be synchronized not only with light, but also with serotonergic activation. Serotonergic agonists and serotonin reuptake inhibitors (e.g., fluoxetine) have a non-photic influence (shifting effects during daytime and attenuation of photic resetting during nighttime) on hamsters' and mice' main clock. Surprisingly, in rats serotonergic modulation of the clock shows essentially photic-like features in vivo (shifting effects during nighttime). To delineate this apparent paradox, we analyzed the effects of fluoxetine and serotonin agonists on rats' clock. First, fluoxetine induced behavioral phase-advances associated with down-regulated expression of the clock genes Per1 and Rorbeta and up-regulated expression of Rev-erbalpha during daytime. Moreover, fluoxetine produced an attenuation of light-induced phase-advances in association with altered expression of Per1, Per2 and Rorbeta during nighttime. Second, we showed that 5-HT(1A) receptors -maybe with co-activation of 5-HT(7) receptors- were implicated in non-photic effects on the main clock. By contrast, 5-HT(3) and 5-HT(2C) receptors were involved in photic-like effects and, for 5-HT(2C) subtype only, in potentiation of photic resetting. Thus this study demonstrates that as for other nocturnal rodents, a global activation of the serotonergic system induces non-photic effects in the rats' clock during daytime and nighttime.
Cuesta
Marc
M
Département de Neurobiologie des Rythmes, Institut de Neurosciences Cellulaires et Intégratives, UPR3212, Centre National de la Recherche Scientifique, Université de Strasbourg, Strasbourg, France.
Clesse
Daniel
D
Pévet
Paul
P
Challet
Etienne
E
D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000235:genetics*; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics*; D003624:Darkness; D005473:Fluoxetine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008027:Light; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D057095:Nuclear Receptor Subfamily 1, Group F, Member 2; D056950:Period Circadian Proteins; D051381:Rats; D020318:Rats, Long-Evans; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
D005473:Fluoxetine; D047908:Intracellular Signaling Peptides and Proteins; D057095:Nuclear Receptor Subfamily 1, Group F, Member 2; D056950:Period Circadian Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011985:Receptors, Serotonin; D012701:Serotonin; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C539023:Per1 protein, mouse; C539024:Per1 protein, rat; C539741:Rorb protein, mouse