Abstract
5-HT and agonists of the 5-HT receptor can modify the response of the mammalian pacemaker, which is located in the hypothalamic suprachiasmatic nuclei (SCN), to photic and nonphotic stimulation. Previous studies suggest that the 5-HT 7 receptor is involved in the regulation of photic input, and the modulation of nonphotic circadian resetting of the circadian clock. The present study investigated the role of the 5-HT 7 receptor by evaluating a wide variety of circadian parameters in mice lacking a functional allele for this receptor (5-HT 7 knockout (KO)) compared with wild type (WT) animals that were bred on the same genetic background, including rate of entrainment, photic responsiveness and nonphotic response to a serotonergic agonist. No significant differences were detected in the average number of days 5-HT 7 KO mice needed to reach entrainment to an advance of 6 h in the LD cycle compared with WT animals. Further, we investigated the acute responsiveness of both groups of mice to acute light stimulation at various times (circadian time (CT) 0, 6, 9, 12, 14, 16, 18, 20 and 22). A significant difference in the phase resetting response to light between the groups was revealed at CT22. Finally, as the 5-HT 7 receptor has been associated with the modulation of nonphotic resetting in vitro, we examined the response of the 5-HT 7 KO mice to systemic administration of a 5-HT 1A/7 agonist. The current study is the first to demonstrate the elimination of a nonphotic response to (+) 8-hydroxy-2-(di- n-propylamino) tetralin (8-OH-DPAT) in mice lacking the 5-HT 7 receptor compared with WT animals in vivo. Taken together, the present findings provide additional evidence that reform the established view on the role of the 5-HT 7 in the photic regulation of retinohypothalamic (RHT) input, and support further the involvement of the 5-HT 7 receptor in the modulation of nonphotic resetting in circadian clock.
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