TY - JOUR T1 - Promotion of Non-Rapid Eye Movement Sleep and Activation of Reticular Thalamic Neurons by a Novel MT<sub>2</sub> Melatonin Receptor Ligand JF - The Journal of Neuroscience JO - J. Neurosci. SP - 18439 LP - 18452 DO - 10.1523/JNEUROSCI.2676-11.2011 VL - 31 IS - 50 AU - Rafael Ochoa-Sanchez AU - Stefano Comai AU - Baptiste Lacoste AU - Francis Rodriguez Bambico AU - Sergio Dominguez-Lopez AU - Gilberto Spadoni AU - Silvia Rivara AU - Annalida Bedini AU - Debora Angeloni AU - Franco Fraschini AU - Marco Mor AU - Giorgio Tarzia AU - Laurent Descarries AU - Gabriella Gobbi Y1 - 2011/12/14 UR - http://www.jneurosci.org/content/31/50/18439.abstract N2 - 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 of NREMS by UCM765 is nullified by the pharmacological blockade or genetic deletion of MT2 receptors. MT2, but not MT1, knock-out mice show a decrease in NREMS compared to the wild strain. Immunohistochemical labeling reveals that MT2 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. ER -