5-HT3 receptor-mediated photic-like responses of the circadian clock in the rat.
Serotonin (5-HT) and 5-HT agonists have various resetting effects on the master clock, located in the suprachiasmatic nucleus (SCN), depending on the species. In rats, they induce photic-like effects on both locomotor activity rhythms and gene expression in the SCN. The 5-HT receptor(s) mediating these effects at circadian time 22 are localized in the SCN, most likely at a presynaptic level, on the retinohypothalamic terminals (RHT) known to convey photic information by releasing glutamate. Indeed, RHT degeneration blocks photic-like effects of a non-specific 5-HT agonist, quipazine. However, the 5-HT receptor subtype(s) involved is still unknown, although 5-HT(3) receptor activation is known to induce glutamate release. We thus analyzed the effects of selective 5-HT(3) agonist and antagonist, as well as a specific NMDA receptor antagonist, on different parameters of the clock. This study shows that the 5-HT(3) receptor mediates the resetting effects of quipazine on locomotor activity rhythms. The 5-HT(3) receptor is only partially implicated in quipazine-induced expression of c-FOS, while NMDA receptor inhibition blocks quipazine photic-like effects on both parameters. Taken together, photic-like responses produced by 5-HT stimulation in rats are likely mediated by (presynaptic?) 5-HT(3) receptor activation followed by NMDA receptor activation.
Graff
Caroline
C
Department of Animal Physiology, Institute of Biology, University of Stuttgart, Pfaffenwaldring 57, 70550 Stuttgart, Germany. carograff@yahoo.fr
Challet
Etienne
E
Pévet
Paul
P
Wollnik
Franziska
F
D000704:Analysis of Variance; D000818:Animals; D056926:CLOCK Proteins; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology / Q000528:radiation effects; D017403:In Situ Hybridization; D008027:Light; D008297:Male; D008954:Models, Biological; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology; D013493:Suprachiasmatic Nucleus / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D016760:Proto-Oncogene Proteins c-fos; D044406:Receptors, Serotonin, 5-HT3; D018490:Serotonin Agents; D015534:Trans-Activators; D016291:Dizocilpine Maleate; D056926:CLOCK Proteins; C538945:Clock protein, rat