RGD Reference Report - Promotion of non-rapid eye movement sleep and activation of reticular thalamic neurons by a novel MT2 melatonin receptor ligand. - Rat Genome Database

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Promotion of non-rapid eye movement sleep and activation of reticular thalamic neurons by a novel MT2 melatonin receptor ligand.

Authors: Ochoa-Sanchez, R  Comai, S  Lacoste, B  Bambico, FR  Dominguez-Lopez, S  Spadoni, G  Rivara, S  Bedini, A  Angeloni, D  Fraschini, F  Mor, M  Tarzia, G  Descarries, L  Gobbi, G 
Citation: Ochoa-Sanchez R, etal., J Neurosci. 2011 Dec 14;31(50):18439-52. doi: 10.1523/JNEUROSCI.2676-11.2011.
RGD ID: 9588665
Pubmed: PMID:22171046   (View Abstract at PubMed)
PMCID: PMC6623882   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.2676-11.2011   (Journal Full-text)

Melatonin activates two brain G-protein coupled receptors, MT(1) and MT(2), whose differential roles in the sleep-wake cycle remain to be defined. The novel MT(2) 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 MT(2) receptors. MT(2), but not MT(1), knock-out mice show a decrease in NREMS compared to the wild strain. Immunohistochemical labeling reveals that MT(2) 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 MT(2) antagonist 4-phenyl-2-propionamidotetralin. Since developing hypnotics that increase NREMS without altering sleep architecture remains a medical challenge, MT(2) receptors may represent a novel target for the treatment of sleep disorders.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Mtnr1b  (melatonin receptor 1B)


Additional Information