title: Systemic administration and local microinjection into the central nervous system of the 5-HT(7) receptor agonist LP-211 modify the sleep-wake cycle in the rat.
abstract: The effects of LP-211, a selective serotonin 5-HT7 receptor agonist were studied in adult rats implanted for chronic sleep recordings. Intraperitoneal administration of LP-211 (2.5-10mg/kg) during the light phase of the light-dark cycle significantly increased wakefulness (W) and reduced rapid-eye-movement sleep (REMS) and the number of REM periods during the 6-h recording period. Direct infusion of LP-211 into the dorsal raphe nucleus (DRN) (2-6 mM), locus coeruleus nucleus (LC) (4 mM), basal forebrain (horizontal limb of the diagonal band of Broca) (HDB) (2 mM) or laterodorsal tegmental nucleus (LDT) (4 mM) induced also a decrease of REMS. Additionally, microinjection of the 5-HT7 receptor ligand into the HDB (2 mM) augmented W. Presently, there is no satisfactory explanation for the effect of 5-HT7 receptor activation on W and REMS occurrence. Additional studies are required to characterize the neurotransmitter systems responsible for the actions of LP-211 on the behavioral states.
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine Clinics Hospital, Montevideo 11600, Uruguay. Electronic address: jmonti@mednet.org.uy.
authors.forename: Jaime M
authors.initials: JM
authors.lastname: Monti
authors.affiliation: Dipartimento Farmaco-Chimico, Universitá degli Study di Bari, Via Orabona, 4, 70125 Bari, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Leopoldo
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine Clinics Hospital, Montevideo 11600, Uruguay.
authors.forename: Héctor
authors.initials: H
authors.lastname: Jantos
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000187:drug effects*; D002940:Circadian Rhythm / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004576:Electromyography; D008297:Male; D008845:Microinjections; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects
chemical_list: C573815:N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide; D010879:Piperazines; D017366:Serotonin Receptor Agonists
keywords: 5-HT; 5-HT(7) receptor; BFB; Basal forebrain; CNS; DRN; Dorsal raphe nucleus; EEG; EMG; GABA; HDB; LC; LDT; LDT/PPT; LP-211; LS; Locus coeruleus nucleus; PRF; REMS; SCN; SWS; Serotonin; W; basal forebrain; central nervous system; dorsal raphe nucleus; electroencephalogram; electromyogram; horizontal limb of the diagonal band of Broca; laterodorsal and pedunculopontine tegmental nuclei; laterodorsal tegmental nucleus; light sleep; locus coeruleus nucleus; pontine reticular formation; rapid-eye-movement sleep; serotonin; slow wave sleep; suprachiasmatic nucleus; wakefulness; γ-aminobutyric acid