Circadian Rhythms of Dopamine and Dihydroxyphenyl Acetic Acid in the Mouse Striatum: Effects of Pinealectomy and of Melatonin Treatment

Abstract

The existence of dopamine (DA)-melatonin (aMT) relationships is well documented in several brain areas of the mammalian central nervous system such as the retina and hypothalamus or the nigrostriatal system. For instance, aMT tempers 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced nigrostriatal damage in C57BL/6 mice. In this mouse strain however, rhythmic production of aMT and its possible interaction with striatal DA is still unclear. In the present work we investigated circadian variations in pineal production of aMT and striatal DA levels in C57BL/6 mice. Effects of pinealectomy and aMT administration were also assessed. Intact, pinealectomized and pinealectomized + aMT-treated mice and their respective control groups were sacrificed at six different times during the 24-hour period. In control animals, aMT displayed a circadian rhythm with a narrow peak at midnight. The peak of aMT coincided with the nadir of the DA rhythm present in the striatum. Shortly after the decrease of DA levels, an increase in 3,4-dihydroxyphenylacetic acid (DOPAC), the main DA metabolite, was observed. The rhythmic changes of DA and DOPAC levels in the striatum were blunted by pinealectomy, whereas administration of aMT (0.1–10 mg/kg) during 6 days to pinealectomized mice restored the rhythms in a dose-dependent manner. Striatal levels of 3-methoxytyramine and homovanillic acid did not change during the 24-hour cycle. The serotonergic system, assessed by the determination of 5-hydroxytryptamine and 5-hydroxyindole-3-acetic acid concentration in striatum, did not show significant time-dependent changes in control animals and was not affected by pinealectomy or aMT treatment. These data substantiate the existence of a link between pineal function, melatonin secretion and DA circadian rhythm in the mouse striatum.

Synergistic effects of melatonin and deprenyl against MPTP-induced mitochondrial damage and DA depletion

“…These results may reflect a modulation of striatal DA turnover by melatonin [33]. Anyway, the synergy between melatonin and deprenyl may depend on several factors.…”

Investigation of Unmedicated Early Onset Restless Legs Syndrome by Voxel-Based Morphometry, T2 Relaxometry, and Functional MR Imaging during the Night-Time Hours

“…25 Dopamine is a catecholamine neurotransmitter exhibiting a circadian rhythm of signaling with a nadir in the night hours. 35 A hypothetic explanation is that patients with RLS may present with night hypofunctioning of the dopamine signaling in the basal ganglia circuitry, which may induce subnormal activation of the D2 receptors of the striatum, resulting in increased activation of the latter. An increase of the GABAergic inhibitory projection from the striatum to the globus pallidus external may be followed by a decrease of the GABAergic inhibitory projection from the globus pallidus external to the STN, which additionally continues to receive excitatory drive from the cortex.…”

Circadian genes, rhythms and the biology of mood disorders

“…Indeed some of the major neurotransmitters that have been implicated in mood regulation, including serotonin, norepinephrine and dopamine, have a circadian rhythm in their levels, release, and synthesis-related enzymes (Weiner et al, 1992;Shieh et al, 1997;Aston-Jones et al, 2001;Barassin et al, 2002;Khaldy et al, 2002;Castaneda et al, 2004;Weber et al, 2004;Malek et al, 2005). There are also circadian rhythms in the expression and activity of several of the receptors that bind these neurotransmitters, suggesting that these entire circuits are under circadian control (Kafka et al, 1983;Wesemann and Weiner, 1990;Witte and Lemmer, 1991;Coon et al, 1997;Akhisaroglu et al, 2005).…”