{Reference Type}: Journal Article
{Title}: Selective Enhancement of REM Sleep in Male Rats through Activation of Melatonin MT1 Receptors Located in the Locus Ceruleus Norepinephrine Neurons.
{Author}: López-Canul M;He Q;Sasson T;Ettaoussi M;Gregorio D;Ochoa-Sanchez R;Catoire H;Posa L;Rouleau G;Beaulieu JM;Comai S;Gobbi G;
{Journal}: J Neurosci
{Volume}: 44
{Issue}: 29
{Year}: 2024 Jul 17
{Factor}: 6.709
{DOI}: 10.1523/JNEUROSCI.0914-23.2024
{Abstract}: 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 MT1 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 MT1 receptors. The increase of REMS duration and the inhibition of LC-NE neuronal activity by UCM871 were abolished by MT1 pharmacological antagonism and by an adeno-associated viral (AAV) vector, which selectively knocked down MT1 receptors in the LC-NE neurons. In conclusion, MT1 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.