Promotion of Non-Rapid Eye Movement Sleep and Activation of Reticular Thalamic Neurons by a Novel MT2 Melatonin Receptor Ligand
Articolo
Data di Pubblicazione:
2011
Citazione:
Promotion of Non-Rapid Eye Movement Sleep and
Activation of Reticular Thalamic Neurons
by a Novel MT2 Melatonin Receptor Ligand / R. Ochoa Sanchez, S. Comai, B. Lacoste, F. Rodriguez Bambico, S. Dominguez Lopez, G. Spadoni, S. Rivara, A. Bedini, D. Angeloni, F. Fraschini, M. Mor, G. Tarzia, L. Descarries, G. Gobbi. - In: THE JOURNAL OF NEUROSCIENCE. - ISSN 0270-6474. - 31:50(2011), pp. 18439-18452.
Abstract:
Melatonin activates two brain G-protein coupled receptors, MT1 and MT2 , whose differential roles in the sleep–wake cycle remain to be
defined. The novel MT2 receptor partial agonist, N-{2-[(3-methoxyphenyl) phenylamino] ethyl} acetamide (UCM765), is here shown to
selectively promote non-rapid eye movement sleep (NREMS) in rats and mice. The enhancement ofNREMSby UCM765 is nullified by the
pharmacological blockade or genetic deletion ofMT2 receptors.MT2 , but notMT1 , knock-out mice show a decrease inNREMScompared
to the wild strain. Immunohistochemical labeling reveals thatMT2 receptors are localized in sleep-related brain regions, and notably the
reticular thalamic nucleus (Rt). Microinfusion of UCM765 in the Rt promotes NREMS, and its systemic administration induces an
increase in firing and rhythmic burst activity of Rt neurons, which is blocked by the MT2 antagonist 4-phenyl-2-propionamidotetralin.
Since developing hypnotics that increase NREMS without altering sleep architecture remains a medical challenge, MT2 receptors may
represent a novel target for the treatment of sleep disorders
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
R. Ochoa Sanchez, S. Comai, B. Lacoste, F. Rodriguez Bambico, S. Dominguez Lopez, G. Spadoni, S. Rivara, A. Bedini, D. Angeloni, F. Fraschini, M. Mor, G. Tarzia, L. Descarries, G. Gobbi
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