Doyle Susan E, Grace Michael S, McIvor Wilson, Menaker Michael
Department of Biology and NSF Center for Biological Timing, University of Virginia, Charlottesville 22903, USA.
Vis Neurosci. 2002 Sep-Oct;19(5):593-601. doi: 10.1017/s0952523802195058.
Both dopamine and melatonin are important for the regulation of retinal rhythmicity, and substantial evidence suggests that these two substances are mutually inhibitory factors that act as chemical analogs of day and night. A circadian oscillator in the mammalian retina regulates melatonin synthesis. Here we show a circadian rhythm of retinal dopamine content in the mouse retina, and examine the role of melatonin in its control. Using high-performance liquid chromatography (HPLC), we measured levels of dopamine and its two major metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in retinas of C3H+/+ mice (which make melatonin) and C57BL/6J mice that are genetically incapable of melatonin synthesis. In a light/dark cycle both strains of mice exhibited daily rhythms of retinal dopamine, DOPAC, and HVA content. However, after 10 days in constant darkness (DD), a circadian rhythm in dopamine levels was present in C3H, but not in C57 mice. C57 mice given ten daily injections of melatonin in DD exhibited a robust circadian rhythm of retinal dopamine content whereas no such rhythm was present in saline-injected controls. Our results demonstrate that (1) a circadian clock generates rhythms of dopamine content in the C3H mouse retina, (2) mice lacking melatonin also lack circadian rhythms of dopamine content, and (3) dopamine rhythms can be generated in these mice by cyclic administration of exogenous melatonin. Our results also indicate that circadian rhythms of retinal dopamine depend upon the rhythmic presence of melatonin, but that cyclic light can drive dopamine rhythms in the absence of melatonin.
多巴胺和褪黑素对于视网膜节律的调节都很重要，大量证据表明这两种物质是相互抑制的因子，起着昼夜化学类似物的作用。哺乳动物视网膜中的昼夜节律振荡器调节褪黑素的合成。在此，我们展示了小鼠视网膜中多巴胺含量的昼夜节律，并研究了褪黑素在其调控中的作用。我们使用高效液相色谱法（HPLC），测量了C3H+/+小鼠（能合成褪黑素）和基因上无法合成褪黑素的C57BL/6J小鼠视网膜中多巴胺及其两种主要代谢产物3,4-二羟基苯乙酸（DOPAC）和高香草酸（HVA）的水平。在光/暗周期中，两种品系的小鼠视网膜多巴胺、DOPAC和HVA含量均呈现每日节律。然而，在持续黑暗（DD）环境中饲养10天后，C3H小鼠的多巴胺水平存在昼夜节律，而C57小鼠则没有。在DD环境中每天注射十次褪黑素的C57小鼠，其视网膜多巴胺含量呈现出强烈的昼夜节律，而注射生理盐水的对照组则没有这种节律。我们的结果表明：（1）昼夜节律时钟在C3H小鼠视网膜中产生多巴胺含量的节律；（2）缺乏褪黑素的小鼠也缺乏多巴胺含量的昼夜节律；（3）通过周期性给予外源性褪黑素，可在这些小鼠中产生多巴胺节律。我们的结果还表明，视网膜多巴胺的昼夜节律依赖于褪黑素的节律性存在，但在没有褪黑素的情况下，周期性光照可驱动多巴胺节律。
