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.
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