title: Melatonin, selective and non-selective MT1/MT2 receptors agonists: differential effects on the 24-h vigilance states.
abstract: Melatonin (MLT) is a neurohormone implicated in several physiological processes such as sleep. Contrasting results have been produced on whether or not it may act as a hypnotic agent, and the neurobiological mechanism through which it controls the vigilance states has not yet been elucidated. In this study we investigated the effect of MLT (40 mg/kg), a non-selective MT1/MT2 receptor agonist (UCM793, 40 mg/kg), and a selective MT2 partial agonist (UCM924, 40 mg/kg) on the 24-h vigilance states. EEG and EMG sleep-wake patterns were registered across the 24-h light-dark cycle in adult Sprague-Dawley male rats. MLT decreased (-37%) the latency to the first episode of non rapid eye movement sleep (NREMS), enhanced the power of NREMS delta band (+33%), but did not alter the duration of any of the three vigilance states. Differently, UCM793 increased the number of episodes (+52%) and decreased the length of the episodes (-38%) of wakefulness but did not alter the 24-h duration of wakefulness, NREMS and REMS. UCM924 instead reduced the latency (-56%) and increased (+31%) the duration of NREMS. Moreover, it raised the number of REMS episodes (+57%) but did not affect REMS duration. Taken together, these findings show that MLT and non-selective MT1/MT2 receptor agonists do not increase the quantity of sleep but differently influence the three vigilance states. In addition, they support the evidence that selective MT2 receptor agonists increase NREMS duration compared to MLT and non-selective MT1/MT2 agonists.
authors.affiliation: Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University Health Center, McGill University, Montreal, QC, Canada.
authors.forename: Rafael
authors.initials: R
authors.lastname: Ochoa-Sanchez
authors.affiliation: Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University Health Center, McGill University, Montreal, QC, Canada.
authors.forename: Stefano
authors.initials: S
authors.lastname: Comai
authors.affiliation: Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino, PU, Italy.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Spadoni
authors.affiliation: Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino, PU, Italy.
authors.forename: Annalida
authors.initials: A
authors.lastname: Bedini
authors.affiliation: Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino, PU, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Tarzia
authors.affiliation: Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University Health Center, McGill University, Montreal, QC, Canada. Electronic address: gabriella.gobbi@mcgill.ca.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gobbi
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D054333:Drug Partial Agonism; D004569:Electroencephalography; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D044122:Receptor, Melatonin, MT1 / Q000819:agonists*; D044123:Receptor, Melatonin, MT2 / Q000819:agonists*; D012894:Sleep Stages / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects*
chemical_list: D000081:Acetamides; D000814:Aniline Compounds; C545681:N-(2-((3-bromophenyl)-(4-fluorophenyl)amino)ethyl)acetamide; C000592134:N-(2-((3-methoxyphenyl)methylamino)ethyl)acetamide); D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D008550:Melatonin
keywords: MT(1) receptor; MT(2) receptor; Melatonin; Sleep–wake cycle; UCM793; UCM924