Circadian-dependent effect of melatonin on dopaminergic D2 antagonist-induced hypokinesia and agonist-induced stereotypies in rats

Sumaya, Isabel C.; Byers, Donna M.; Irwin, Louis N.; Val, Stéphanie; Moss, Donald E.

doi:10.1016/j.pbb.2004.05.014

Cited by 16 publications

(7 citation statements)

References 35 publications

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“…Furthermore, we found that melatonin markedly inhibited the compensatory upregulation of rotenone-induced D2R. There are consistent reports demonstrating that melatonin treatment reduced apomorphine (D2 agonist)-induced stereotypies [47] and afforded full prevention against methamphetamine-induced depletion of DAT binding [48]. These findings indicated that the protective action of melatonin also preserved dopamine synaptic transmission of nerve terminals in the striatum.…”

Section: Discussionsupporting

confidence: 86%

Melatonin reduces the neuronal loss, downregulation of dopamine transporter, and upregulation of D2 receptor in rotenone‐induced parkinsonian rats

Lin¹,

Huang²,

Ching³

et al. 2007

Journal of Pineal Research

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Parkinson's disease (PD) is a movement disorder resulting from nigrostriatal dopaminergic neurodegeneration. The impairment of mitochondrial function and dopamine synaptic transmission are involved in the pathogenesis of PD. Two mitochondrial inhibitors, 1-methyl-4-phenylpyridine (MPP(+)) and rotenone, have been used to induce dopaminergic neuronal death both in in vitro and in vivo models of PD. Because the uptake of MPP(+) is mediated by the dopamine transporter (DAT), we used a cell-permeable rotenone-induced PD model to investigate the role of DAT and dopamine D2 receptor (D2R) on dopaminergic neuronal loss. Rotenone subcutaneously infused for 14 days induced PD symptoms in rats, as indicated by reduced spontaneous locomotor activity (hypokinesis), loss of tyrosine hydroxylase (TH, a marker enzyme for dopamine neurons) immunoreactivity in the substantia nigra and striatum, obvious alpha-synuclein accumulation, downregulated DAT protein expression, and upregulated D2R expression. Interestingly, rotenone also caused significant noradrenergic neuronal loss in the locus coeruleus. Melatonin, an antioxidant, prevented nigrostriatal neurodegeneration and alpha-synuclein aggregation without affecting the rotenone-induced weight loss and hypokinesis. However, rotenone-induced hypokinesis was markedly reversed by the DAT antagonist nomifensine and body weight loss was attenuated by the D2R antagonist sulpiride. In addition, both antagonists significantly prevented the reduction of striatal TH or DAT immunoreactivity but not the loss of nigral TH- and DAT-immunopositive neurons. These results suggested that oxidative stress and DAT downregulation are involved in the rotenone-induced pathogenesis of nigrostriatal dopaminergic neurodegeneration, whereas D2R upregulation may simply represent a compensatory response.

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Section: Discussionsupporting

confidence: 86%

Melatonin reduces the neuronal loss, downregulation of dopamine transporter, and upregulation of D2 receptor in rotenone‐induced parkinsonian rats

Lin¹,

Huang²,

Ching³

et al. 2007

Journal of Pineal Research

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“…125 I]sulpiride binding in the striatum during the dark phase (38), larger responses to apomorphine during the dark phase in rats (44), and larger reflexive locomotor responses to quinpirole during the dark in Drosophila melanogaster (45).…”

Section: Discussionmentioning

confidence: 99%

Dopamine transporters govern diurnal variation in extracellular dopamine tone

Ferris

España

Locke

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

163

135

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The majority of neurotransmitter systems shows variations in state-dependent cell firing rates that are mechanistically linked to variations in extracellular levels, or tone, of their respective neurotransmitter. Diurnal variation in dopamine tone has also been demonstrated within the striatum, but this neurotransmitter is unique, in that variation in dopamine tone is likely not related to dopamine cell firing; this is largely because of the observation that midbrain dopamine neurons do not display diurnal fluctuations in firing rates. Therefore, we conducted a systematic investigation of possible mechanisms for the variation in extracellular dopamine tone. Using microdialysis and fast-scan cyclic voltammetry in rats, as well as wild-type and dopamine transporter (DAT) knock-out mice, we demonstrate that dopamine uptake through the DAT and the magnitude of subsecond dopamine release is inversely related to the magnitude of extracellular dopamine tone. We investigated dopamine metabolism, uptake, release, D2 autoreceptor sensitivity, and tyrosine hydroxylase expression and activity as mechanisms for this variation. Using this approach, we have pinpointed the DAT as a critical governor of diurnal variation in extracellular dopamine tone and, as a consequence, influencing the magnitude of electrically stimulated dopamine release. Understanding diurnal variation in dopamine tone is critical for understanding and treating the multitude of psychiatric disorders that originate from perturbations of the dopamine system. circadian | caudate-putamen | nucleus accumbens T he dopamine transporter (DAT) is a transmembrane protein that removes dopamine (DA) from the extracellular space to terminate signaling at pre-and postsynaptic receptors. Extensive evidence indicates that aberrant DAT function may be involved in many neuropsychiatric illnesses, including attention deficit hyperactivity disorder (1, 2), depression (3, 4), substance abuse disorders (5, 6), schizophrenia (7-9), and anxiety disorders (10, 11). Our current understanding of the role of the DAT under physiologically normal conditions is that of a homeostatic regulator. This basic hypothesis was confirmed in work using DAT knock-out (KO) mice, where extracellular DA levels ([DA] ext ) and corresponding locomotor activity are substantially higher than in WT animals (12, 13). In addition, up-or down-regulation of the DAT is regarded as a compensatory plasticity to "normalize" [DA] ext in the context of repeated exposure to abused drugs (5,14,15).Despite this progress in understanding DAT function, much less work has been dedicated to understanding the role of the DAT and other presynaptic modulators of [DA] Despite the limited mechanistic understanding of the complex relationship between [DA] ext and nerve terminal function, behaviors known to be governed by DA are strongly influenced by diurnal cycles. For example, behaviors that measure reinforcement and reward, such as psychostimulant self-administration and conditioned place preference, fluctuate markedly a...

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“…The anti-nociception pathway elicited by melatonin in rodents is complex with involvement of opioid, serotonin, acetylcholine, dopamine, α-adrenoceptor and arginine-NO receptors (Mantovani et al 2006;Shin et al 2011). Melatonin reduces hypokinesis and stereotypies induced by D2 ligands and has a synergistic effect with apomorphine in the mouse tail suspension test (Sumaya et al 2004;Binfare et al 2010). Melatonin induced hypothermia in rats is significantly reduced by treatment with either a 5-HT 2A receptor agonist or 5-HT 1A receptor antagonist (Lin and Chuang 2002).…”

Section: Discussionmentioning

confidence: 99%

Dampening of neurotransmitter action: molecular similarity within the melatonin structure

Williams

2018

Endocrine Regulations

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Objectives.Melatonin initiates physiologic and therapeutic responses in various tissues through binding to poorly defined MT receptors regulated by G-proteins and purine nucleotides. Melatonin's interaction with other G-protein regulated receptors, including those of serotonin, is unclear. This study explores the potential for the interaction of melatonin with nucleotide and receptor ligand structures.Methods. The study uses a computational program to investigate relative molecular similarity by the comparative superimposition and quantitative fitting of molecular structures to adenine and guanine nucleotide templates.Results. A minimum energy melatonin conformer replicates the nucleotide fits of ligand structures that regulate Gα i and Gα q proteins via serotonin, dopamine, opioid, α-adrenoceptor, and muscarinic receptor classes. The same conformer also replicates the nucleotide fits of ligand structures regulating K + and Ca 2+ ion channels. The acyl-methoxy distance within the melatonin conformer matches a carbonyl-hydroxyl distance in guanine nucleotide.Conclusion. Molecular similarity within the melatonin and ligand structures relates to the established effects of melatonin on cell receptors regulated by purine nucleotides in cell signal transduction processes. Pharmacologic receptor promiscuity may contribute to the widespread effects of melatonin.

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Circadian-dependent effect of melatonin on dopaminergic D2 antagonist-induced hypokinesia and agonist-induced stereotypies in rats

Cited by 16 publications

References 35 publications

Melatonin reduces the neuronal loss, downregulation of dopamine transporter, and upregulation of D2 receptor in rotenone‐induced parkinsonian rats

Melatonin reduces the neuronal loss, downregulation of dopamine transporter, and upregulation of D2 receptor in rotenone‐induced parkinsonian rats

Dopamine transporters govern diurnal variation in extracellular dopamine tone

Dampening of neurotransmitter action: molecular similarity within the melatonin structure

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