title: Clonidine induces sedation through acting on the perifornical area and the locus coeruleus in rats.
abstract: BACKGROUND
  The main target site of action for the sedative clonidine (CLO), an α2 adrenoceptor agonist, has been considered to be the locus coeruleus (LC). However, previous reports suggest other sites of action of CLO than the LC. Our previous studies suggested that the neuronal activities in the perifornical area (Pef) could influence the sedative or the anesthetic level induced by anesthetics. Therefore, we examined whether microinjection of CLO into the Pef might induce sedation in rats.
  
  
  METHODS
  Fifty-five Wistar rats were used. The cortical norepinephrine (NE) and acetylcholine (ACh) effluxes were detected using microdialysis and measured by high-performance liquid chromatography in samples collected every 20 minutes. First, we injected CLO (100, 300, and 1000 μg/kg cumulative doses) intraperitoneally (IP) and observed the changes in NE or ACh efflux. Second, we injected CLO (4.8 μg in 0.2 μL) or saline (0.2 μL) into the LC or the Pef and observed the changes in NE or ACh efflux for 2 hours. Finally, a sedative/anesthetic score was obtained after IP, LC or Pef microinjection of CLO.
  
  
  RESULTS
  IP injection of CLO induced sedation and resulted in a dose-dependent attenuation of the cortical effluxes of both NE and ACh (P<0.001). Microinjection of CLO either into the LC or the Pef induced sedation and significantly decreased the cortical NE efflux (P<0.001). Cortical ACh efflux was significantly reduced by microinjection of CLO into the Pef but not by microinjection into the LC (P<0.05).
  
  
  CONCLUSIONS
  The Pef and the LC are responsible for the sedative action of CLO in rats.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Fukuda
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Minakawa
authors.forename: Shigehito
authors.initials: S
authors.lastname: Sawamura
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology*; D003627:Data Interpretation, Statistical; D020712:Fornix, Brain / Q000502:physiology*; D006993:Hypnotics and Sedatives; D008125:Locus Coeruleus / Q000502:physiology*; D008297:Male; D008845:Microinjections; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000316:Adrenergic alpha-Agonists; D006993:Hypnotics and Sedatives; D003000:Clonidine; D000109:Acetylcholine; D009638:Norepinephrine