Smith M I, Piper D C, Duxon M S, Upton N
Neurology-CEDD, GlaxoSmithkline, New Frontiers Science Park North, Third Avenue, Harlow, Essex, UK, CM19 5AW.
Neurosci Lett. 2003 May 8;341(3):256-8. doi: 10.1016/s0304-3940(03)00066-1.
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.
