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-HT3 receptor activation is known to induce glutamate release. We thus analyzed the effects of selective 5-HT3 agonist and antagonist, as well as a specific NMDA receptor antagonist, on different parameters of the clock. This study shows that the 5-HT3 receptor mediates the resetting effects of quipazine on locomotor activity rhythms. The 5-HT3 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-HT3 receptor activation followed by NMDA receptor activation.