Gardani M, Biello S M
Department of Psychology, University of Glasgow, 58 Hillhead Street, Glasgow, G12 8QB, UK.
Neuroscience. 2008 Mar 3;152(1):245-53. doi: 10.1016/j.neuroscience.2007.10.028.
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-HT7 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-HT7 receptor by evaluating a wide variety of circadian parameters in mice lacking a functional allele for this receptor (5-HT7 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-HT7 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-HT7 receptor has been associated with the modulation of nonphotic resetting in vitro, we examined the response of the 5-HT7 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-HT7 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-HT7 in the photic regulation of retinohypothalamic (RHT) input, and support further the involvement of the 5-HT7 receptor in the modulation of nonphotic resetting in circadian clock.
5-羟色胺（5-HT）及其受体激动剂可改变哺乳动物生物钟起搏器的反应，该起搏器位于下丘脑视交叉上核（SCN），对光刺激和非光刺激产生反应。先前的研究表明，5-HT7受体参与光输入的调节以及生物钟非光性昼夜节律重置的调节。本研究通过评估缺乏该受体功能等位基因的小鼠（5-HT7基因敲除（KO））与在相同遗传背景下培育的野生型（WT）动物的多种昼夜节律参数，来研究5-HT7受体的作用，这些参数包括同步化速率、对光的反应性以及对血清素能激动剂的非光反应。与WT动物相比，未检测到5-HT7基因敲除小鼠在LD周期中达到提前6小时同步化所需的平均天数有显著差异。此外，我们研究了两组小鼠在不同时间（昼夜时间（CT）0、6、9、12、14、16、18、20和22）对急性光刺激的急性反应性。在CT22时，两组之间对光的相位重置反应存在显著差异。最后，由于5-HT7受体已被证明在体外参与非光性重置的调节，我们检测了5-HT7基因敲除小鼠对全身给予5-HT(1A/7)激动剂的反应。本研究首次证明，与体内的WT动物相比，缺乏5-HT7受体的小鼠对（+）8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）的非光反应消失。综上所述，本研究结果提供了更多证据，修正了关于5-HT7在视网膜下丘脑（RHT）输入光调节中作用的既定观点，并进一步支持5-HT7受体参与生物钟非光性重置的调节。
