Edgar D M, Reid M S, Dement W C
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, California 94305, USA.
Am J Physiol. 1997 Jul;273(1 Pt 2):R265-9. doi: 10.1152/ajpregu.1997.273.1.R265.
The circadian pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus receives serotonergic afferents from the midbrain raphe nuclei, but the functional role of this projection is unclear. In rodents, locomotor activity increases serotonin content in the SCN, and serotonergic agonists phase shift the circadian clock in a manner closely similar to voluntary bouts of vigorous exercise, suggesting that serotonergic afferents could be part of the activity-dependent entrainment mechanism. We investigated this possibility by selectively lesioning serotonin terminals within and adjacent to the SCN by local microinjection of 5,7-dihydroxytryptamine in mice pretreated with desipramine. This treatment decreased serotonin content 96 +/- 1% and 5-hydroxyindole-3-acetic acid content below levels of detection (nearly 100%) but did not decrease norepinephrine content or neuropeptide Y immunoreactivity in the SCN. These lesions did not alter subsequent running activity levels, yet rendered mice unable to synchronize to a regularly scheduled 2-h wheel running paradigm that entrained sham-lesioned controls. Serotonin afferents are thus necessary for activity-dependent entrainment in the mouse.
位于下丘脑视交叉上核（SCN）的昼夜节律起搏器接收来自中脑缝核的5-羟色胺能传入纤维，但其功能作用尚不清楚。在啮齿动物中，运动活动会增加SCN中的5-羟色胺含量，且5-羟色胺能激动剂会以与剧烈运动的自发发作非常相似的方式使昼夜节律时钟发生相位偏移，这表明5-羟色胺能传入纤维可能是活动依赖性昼夜节律调节机制的一部分。我们通过在接受去甲丙咪嗪预处理的小鼠中局部微量注射5,7-二羟基色胺，选择性地损伤SCN内部及其附近的5-羟色胺能终末，来研究这种可能性。这种处理使5-羟色胺含量降低了96±1%，5-羟吲哚-3-乙酸含量降至检测水平以下（几乎100%），但并未降低SCN中的去甲肾上腺素含量或神经肽Y免疫反应性。这些损伤并未改变随后的跑步活动水平，但使小鼠无法同步到可使假手术对照组产生昼夜节律调节的2小时定时转轮运动模式。因此，5-羟色胺能传入纤维对于小鼠的活动依赖性昼夜节律调节是必需的。
