title: The effects of systemic and local microinjection into the central nervous system of the selective serotonin 5-HT6 receptor agonist WAY-208466 on sleep and wakefulness in the rat.
abstract: The effects of WAY-208466, a selective 5-HT6 receptor agonist on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. Systemic administration of WAY-208466 during the light phase of the light-dark cycle significantly increased wakefulness (W) and reduced slow wave sleep (SWS), REM sleep (REMS) and the number of REMS periods. Pretreatment with the selective 5-HT6 receptor antagonist RO-399885 prevented the effects of the 5-HT6 receptor agonist on W, SWS and REMS. Direct infusion of WAY-208466 into the dorsal raphe nucleus, locus coeruleus, basal forebrain (horizontal limb of the diagonal band of Broca) or laterodorsal tegmental nucleus specifically decreased REMS without significantly altering W or SWS. In all instances the REMS suppression was dependent upon the reduction of REMS periods. The finding that WAY-208466 increases extracellular γ-aminobutyric acid (GABA) levels in the rat frontal cortex tends to suggest that the neurotransmitter could be involved in the 5-HT6 receptor agonist-induced disruption of the sleep-wake cycle. However, further studies are needed to resolve this issue.
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine Clinics Hospital. Montevideo 11600, Uruguay. jmonti@mednet.org.uy
authors.forename: Jaime M
authors.initials: JM
authors.lastname: Monti
authors.forename: Héctor
authors.initials: H
authors.lastname: Jantos
authors.forename: Lee E
authors.initials: LE
authors.lastname: Schechter
mesh_terms: D000818:Animals; D008297:Male; D008744:Methylamines / Q000008:administration & dosage*; D008845:Microinjections / Q000379:methods; D011725:Pyridines / Q000008:administration & dosage*; D011903:Raphe Nuclei / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects*; D014851:Wakefulness / Q000187:drug effects*
chemical_list: D008744:Methylamines; C558330:N-(2-(3-(3-fluorophenylsulfonyl)-1H-pyrrolo(2,3-b)pyridin-1-yl)ethyl)-N,N-dimethylamine; D011725:Pyridines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C097216:serotonin 6 receptor