Melatonin Supports CYP2D-Mediated Serotonin Synthesis in the Brain

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Anna HaduchWładysława A Daniel

Abstract

Melatonin is used in the therapy of sleep and mood disorders and as a neuroprotective agent. The aim of our study was to demonstrate that melatonin supported (via its deacetylation to 5-methoxytryptamine) CYP2D-mediated synthesis of serotonin from 5-methoxytryptamine. We measured serotonin tissue content in some brain regions (the cortex, hippocampus, nucleus accumbens, striatum, thalamus, hypothalamus, brain stem, medulla oblongata, and cerebellum) (model A), as well as its extracellular concentration in the striatum using an in vivo microdialysis (model B) after melatonin injection (100 mg/kg i.p.) to male Wistar rats. Melatonin increased the tissue concentration of serotonin in the brain structures studied of naïve, sham-operated, or serotonergic neurotoxin (5,7-dihydroxytryptamine)-lesioned rats (model A). Intracerebroventricular quinine (a CYP2D inhibitor) prevented the melatonin-induced increase in serotonin concentration. In the presence of pargyline (a monoaminoxidase inhibitor), the effect of melatonin was not visible in the majority of the brain structures studied but could be seen in all of them in 5,7-dihydroxytryptamine-lesioned animals when serotonin storage and synthesis via a classic tryptophan pathway was dimin...Continue Reading

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Citations

Feb 17, 2018·Drug Metabolism Reviews·Cynthia Navarro-MabarakJesús Javier Espinosa-Aguirre
Sep 29, 2017·Frontiers in Cellular Neuroscience·Cristina MiguelezPhilippe De Deurwaerdère
Jun 28, 2019·Frontiers in Endocrinology·Francisco Javier Sánchez-VázquezJesús M Míguez
Dec 29, 2020·Drug Metabolism Reviews·Wojciech Kuban, Władysława Anna Daniel
Jun 14, 2021·Environmental Science and Pollution Research International·Hanan A EdresMohamed S Elfeky

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