PT  - JOURNAL ARTICLE
AU  - Bourgin, Patrice
AU  - Huitrón-Reséndiz, Salvador
AU  - Spier, Avron D.
AU  - Fabre, Véronique
AU  - Morte, Beatriz
AU  - Criado, José R.
AU  - Sutcliffe, J. Gregor
AU  - Henriksen, Steven J.
AU  - de Lecea, Luis
TI  - Hypocretin-1 Modulates Rapid Eye Movement Sleep through Activation of Locus Coeruleus Neurons
AID  - 10.1523/JNEUROSCI.20-20-07760.2000
DP  - 2000 Oct 15
TA  - The Journal of Neuroscience
PG  - 7760--7765
VI  - 20
IP  - 20
4099  - http://www.jneurosci.org/content/20/20/7760.short
4100  - http://www.jneurosci.org/content/20/20/7760.full
SO  - J. Neurosci.2000 Oct 15; 20
AB  - The hypocretins (hcrts), also known as orexins, are two recently identified excitatory neuropeptides that in rat are produced by ∼1200 neurons whose cell bodies are located in the lateral hypothalamus. The hypocretins/orexins have been implicated in the regulation of rapid eye movement (REM) sleep and the pathophysiology of narcolepsy. In the present study, we investigated whether the locus coeruleus (LC), a structure receiving dense hcrtergic innervation, which is quiescent during REM sleep, might be a target for hcrt to regulate REM sleep. Local administration of hcrt1 but not hcrt2 in the LC suppressed REM sleep in a dose-dependent manner and increased wakefulness at the expense of deep, slow-wave sleep. These effects were blocked with an antibody that neutralizes hcrt binding to hcrt receptor 1. In situ hybridization and immunocytochemistry showed the presence of hcrt receptor 1 but not the presence of hcrt receptor 2 in the LC. Iontophoretic application of hcrt1 enhanced the firing rate of LC neurons in vivo, and local injection of hcrt1 into the LC induced the expression of c-fos in the LC area. We propose that hcrt receptor 1 in the LC is a key target for REM sleep regulation and might be involved in the pathophysiological mechanisms of narcolepsy.