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.