Melatonin Supports CYP2D-Mediated Serotonin Synthesis in the Brain

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 diminished. Melatonin alone did not significantly increase extracellular serotonin concentration in the striatum of naïve rats but raised its content in pargyline-pretreated animals (model B). The CYP2D inhibitor propafenone given intrastructurally prevented the melatonin-induced increase in striatal serotonin in those animals. The obtained results indicate that melatonin supports CYP2D-catalyzed serotonin synthesis from 5-methoxytryptamine in the brain in vivo, which closes the serotonin-melatonin-serotonin biochemical cycle. The metabolism of exogenous melatonin to the neurotransmitter serotonin may be regarded as a newly recognized additional component of its pharmacological action.

Healthy lifestyle behaviors are major predictors of mental wellbeing during COVID-19 pandemic confinement: A study on adult Arabs in higher educational institutions

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Environmental Cycles, Melatonin, and Circadian Control of Stress Response in Fish

“…At the level of the hypothalamus-preoptic area, serotonin stimulates the HPI axis by increasing Crh release, which boosts the downstream GC stress response (125, 134). Studies have revealed that melatonin can interact with serotonin to modulate its function (109, 130, 135). Moreover, melatonin ability to reduce stress in teleosts has been usually associated with simultaneous changes in brain serotonergic activity (109, 130, 133).…”

Healthy Lifestyle Behaviors Are Major Predictors of Mental Wellbeing During COVID-19 Pandemic Confinement: A Study on Adult Arabs in Higher Educational Institutions

“…[26]. Recently, in 2020 and due to COVID19 pandemic outbreak and associated con nement, increased levels of psychological problems such as anxiety, depression and poor sleeping quality were found among Chinese quarantined participants [19,20,21]. Furthermore, a recent review concluded that quarantine deteriorate peoples' mental health causing negative psychological effects including post-traumatic stress symptoms [27,28].…”

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