title: The effects of intracerebroventricular application of 8-Br-cGMP and LY-83,583, a guanylyl cyclase inhibitor, on sleep-wake activity in rats.
abstract: Cyclic GMP is the second messenger that mediates most of the neuronal effects of nitric oxide (NO). Several lines of evidence suggest that NO-ergic mechanisms play an integral role in the regulation of vigilance. In the present study, we tested the effects of the activation of cGMP-receptive mechanisms and the inhibitor of guanylyl cyclase (GC), LY-83,583, on sleep in rats. Rats were injected intracerebroventricularly (icv) with 0.16, 4, 100, and 500 microg or 2.5 mg 8-Br-cGMP, a membrane-permeable analogue of cGMP, or 1 and 100 microg LY-83,583. Administration of 4 microg-2.5 mg 8-Br-cGMP increased wakefulness and suppressed rapid-eye-movement sleep (REMS) and non-REMS (NREMS) in rats when given before dark onset but not when given before the light period. The GC inhibitor LY-83,583 strongly promoted NREMS and suppressed REMS during the light period of the day. Furthermore, LY-83,583 induced striking increases in the delta-wave activity of the electroencephalogram (EEG) during NREMS, whereas EEG activity above the 4.5 Hz wave range was suppressed in all vigilance states. Our finding that cGMP has an arousal-promoting activity is in line with the hypothesis that NO/cGMP signaling pathway is involved in the regulation of vigilance.
authors.affiliation: Department of Biological Sciences, Fordham University, 441 E. Fordham Road, Bronx, NY 10458, USA.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Ribeiro
authors.forename: Levente
authors.initials: L
authors.lastname: Kapás
mesh_terms: D000634:Aminoquinolines / Q000008:administration & dosage*; D000818:Animals; D001288:Attention; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004576:Electromyography; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006162:Guanylate Cyclase / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology*; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology*
chemical_list: D000634:Aminoquinolines; D004791:Enzyme Inhibitors; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; C041715:6-anilino-5,8-quinolinedione; D006162:Guanylate Cyclase; D006152:Cyclic GMP