Evidence implicating a role for orexin-1 receptor modulation of paradoxical sleep in the rat.
The neuropeptide orexin-A modulates the sleep-wake cycle such that central administration to rats increases arousal, reduces slow-wave-sleep (SWS) and paradoxical sleep (PS) and delays PS onset. The contribution of orexin-1 and -2 receptor (OXR) activation to this orexin-A response is still unknown. Using the OX(1)R antagonist SB-334867-A we investigated the role of this receptor in orexin-A-induced PS alteration. Male rats prepared for frontal-occipital electroencephalograph, nuchal muscle electromyograph recording and lateral ventricle cannulae received vehicle or orexin-A (10 microg icv) at lights on in combination with vehicle or SB-334867-A (10 or 30 mg/kg ip) 30 min pre-icv injection. The amount of arousal, SWS 1, SWS 2 and PS was determined during the 1st h post icv administration along with the latency to onset of the first> or =10 s epoch of PS. Orexin-A administration reduced the amount and increased the latency to onset of PS. SB-334867-A reversed this effect of orexin-A. The present study demonstrates that the OX(1)R also has a role in orexinergic sleep modulation.
Smith
M I
MI
Neurology-CEDD, GlaxoSmithkline, New Frontiers Science Park North, Third Avenue, Harlow, Essex, UK, CM19 5AW. martin_i_smith@gsk.com
Piper
D C
DC
Duxon
M S
MS
Upton
N
N
D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009287:Naphthyridines; D009479:Neuropeptides / Q000494:pharmacology; D064446:Orexin Receptors; D000068797:Orexins; D051381:Rats; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology*; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009287:Naphthyridines; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D014508:Urea