Selective Enhancement of REM Sleep in Male Rats through Activation of Melatonin MT 1 Receptors Located in the Locus Ceruleus Norepinephrine Neurons.

Autor: López-Canul M; Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec H3A 1A1, Canada., He Q; Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec H3A 1A1, Canada., Sasson T; Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec H3A 1A1, Canada., Ettaoussi M; Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec H3A 1A1, Canada., Gregorio D; Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec H3A 1A1, Canada.; IRCCS San Raffaele Scientific Institute, Milan 20132, Italy., Ochoa-Sanchez R; Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec H3A 1A1, Canada., Catoire H; Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec H3A 2B4, Canada., Posa L; Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec H3A 1A1, Canada., Rouleau G; Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec H3A 2B4, Canada., Beaulieu JM; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario M5G 2C8, Canada., Comai S; Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec H3A 1A1, Canada gabriella.gobbi@mcgill.ca stefano.comai@unipd.it.; IRCCS San Raffaele Scientific Institute, Milan 20132, Italy.; Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua 35131, Italy.; Department of Biomedical Sciences, University of Padua, Padua 35131, Italy., Gobbi G; Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec H3A 1A1, Canada gabriella.gobbi@mcgill.ca stefano.comai@unipd.it.; Research Institute, McGill University Health Center, McGill University, Montreal, Quebec H3A 1A1, Canada.
Jazyk: angličtina
Zdroj: The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2024 Jul 17; Vol. 44 (29). Date of Electronic Publication: 2024 Jul 17.
DOI: 10.1523/JNEUROSCI.0914-23.2024
Abstrakt: Sleep disorders affect millions of people around the world and have a high comorbidity with psychiatric disorders. While current hypnotics mostly increase non-rapid eye movement sleep (NREMS), drugs acting selectively on enhancing rapid eye movement sleep (REMS) are lacking. This polysomnographic study in male rats showed that the first-in-class selective melatonin MT 1 receptor partial agonist UCM871 increases the duration of REMS without affecting that of NREMS. The REMS-promoting effects of UCM871 occurred by inhibiting, in a dose-response manner, the firing activity of the locus ceruleus (LC) norepinephrine (NE) neurons, which express MT 1 receptors. The increase of REMS duration and the inhibition of LC-NE neuronal activity by UCM871 were abolished by MT 1 pharmacological antagonism and by an adeno-associated viral (AAV) vector, which selectively knocked down MT 1 receptors in the LC-NE neurons. In conclusion, MT 1 receptor agonism inhibits LC-NE neurons and triggers REMS, thus representing a novel mechanism and target for REMS disorders and/or psychiatric disorders associated with REMS impairments.
Competing Interests: The authors declare no competing financial interests.
(Copyright © 2024 López-Canul et al.)
Databáze: MEDLINE
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