Horikawa Kazumasa, Shibata Shigenobu
Department of Pharmacology, School of Science and Engineering, Waseda University, Higashifushimi 2-7-5, Nishitokyo-Shi, Tokyo 202-0021, Japan.
Neurosci Lett. 2004 Sep 23;368(2):130-4. doi: 10.1016/j.neulet.2004.06.072.
Several lines of evidence indicate that 5-HT neuronal systems may play a critical role for the non-photic entrainment of the rodent circadian clock. Although it is well established that (+)8-hydroxy-2-(di-n-propylamino)tetralin [(+)8-OH-DPAT], a 5-HT(1A/7) receptor agonist, causes a phase-advance of behavioral rhythm in hamsters, little is known whether this agent produces phase shifts of activity rhythm in mice. Therefore, we examined the effect of (+)8-OH-DPAT on the mouse locomotor activity rhythm. Systemic administration of this chemical at mid-subjective daytime induced a clear and dose-dependent phase advance, while there were no significant phase shifts at other times (early-subjective day, late-subjective day, or subjective night). Additionally, (+)8-OH-DPAT accelerated the re-entrainment of mouse behavioral rhythm to a 6-h advanced light-dark cycle. These results suggest that we can use mice for understanding the molecular mechanism of (+)8-OH-DPAT-induced phase shift because of availability of clock gene targeted mice.
多项证据表明,5-羟色胺(5-HT)神经元系统可能在啮齿动物生物钟的非光信号同步中起关键作用。尽管已经明确,5-HT(1A/7)受体激动剂(+)8-羟基-2-(二正丙基氨基)四氢萘[(+)8-OH-DPAT]会使仓鼠的行为节律提前,但对于该药物是否会使小鼠的活动节律发生相位改变却知之甚少。因此,我们研究了(+)8-OH-DPAT对小鼠运动活动节律的影响。在主观日中午全身给药这种化学物质会引起明显且剂量依赖性的相位提前,而在其他时间(主观日早期、主观日晚期或主观夜)则没有明显的相位改变。此外,(+)8-OH-DPAT加速了小鼠行为节律对提前6小时的明暗周期的重新同步。这些结果表明,由于存在生物钟基因靶向小鼠,我们可以利用小鼠来理解(+)8-OH-DPAT诱导相位改变的分子机制。