title: Substance P and the neurokinin-1 receptor regulate electroencephalogram non-rapid eye movement sleep slow-wave activity locally.
abstract: The neuropeptide substance P is an excitatory neurotransmitter produced by various cells including neurons and microglia that is involved in regulating inflammation and cerebral blood flow--functions that affect sleep and slow-wave activity (SWA). Substance P is the major ligand for the neurokinin-1 receptor (NK-1R), which is found throughout the brain including the cortex. The NK-1R is found on sleep-active cortical neurons expressing neuronal nitric oxide synthase whose activity is associated with SWA. We determined the effects of local cortical administration of a NK-1R agonist (substance P-fragment 1, 7) and a NK-1R antagonist (CP96345) on sleep and SWA in mice. The NK-1R agonist significantly enhanced SWA for several hours when applied locally to the cortex of the ipsilateral hemisphere as the electroencephalogram (EEG) electrode but not after application to the contralateral hemisphere when compared to saline vehicle control injections. In addition, a significant compensatory reduction in SWA was found after the NK-1R agonist-induced enhancements in SWA. Conversely, injections of the NK-1R antagonist into the cortex of the ipsilateral hemisphere of the EEG electrode attenuated SWA compared to vehicle injections but this effect was not found after injections of the NK-1R antagonist into contralateral hemisphere as the EEG electrode. Non-rapid eye movement sleep and rapid eye movement sleep duration responses after NK-1R agonist and antagonist injections were not significantly different from the responses to the vehicle. Our findings indicate that the substance P and the NK-1R are involved in regulating SWA locally.
authors.affiliation: Department of Psychiatry, Harvard Medical School and Veterans Affairs Boston Healthcare System, West Roxbury, MA 02132, USA. Electronic address: Mark_Zielinski@hms.harvard.edu.
authors.forename: M R
authors.initials: MR
authors.lastname: Zielinski
authors.affiliation: Department of Psychiatry, Harvard Medical School and Veterans Affairs Boston Healthcare System, West Roxbury, MA 02132, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Karpova
authors.affiliation: Department of Psychiatry, Harvard Medical School and Veterans Affairs Boston Healthcare System, West Roxbury, MA 02132, USA; Department of Anatomy and Embryology, Peking University Health Science Center, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Psychiatry, Harvard Medical School and Veterans Affairs Boston Healthcare System, West Roxbury, MA 02132, USA.
authors.forename: D
authors.initials: D
authors.lastname: Gerashchenko
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004567:Electrodes, Implanted; D004569:Electroencephalography; D004576:Electromyography; D007839:Functional Laterality / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D017286:Polysomnography; D018040:Receptors, Neurokinin-1 / Q000819:agonists* / Q000378:metabolism; D012894:Sleep Stages / Q000187:drug effects* / Q000502:physiology; D013373:Substance P / Q000494:pharmacology*
chemical_list: D001713:Biphenyl Compounds; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D018040:Receptors, Neurokinin-1; D013373:Substance P; C036877:substance P (1-7); C066892:CP 96345
keywords: local sleep; mice; neurokinin-1 receptor; slow-wave activity; substance P; tachykinin