title: Inhibitory effect of chronic oral treatment with fluoxetine on capsaicin-induced external carotid vasodilatation in anaesthetised dogs.
abstract: BACKGROUND
  During migraine, capsaicin-sensitive trigeminal sensory nerves release calcitonin gene-related peptide (CGRP), resulting in cranial vasodilatation and central nociception. Moreover, 5-HT is involved in the pathophysiology of migraine and depression. Interestingly, some limited lines of evidence suggest that fluoxetine may be effective in migraine prophylaxis, but the underlying mechanisms are uncertain. Hence, this study investigated the canine external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine before and after acute and chronic oral treatment with fluoxetine.
  
  
  METHODS
  Forty-eight vagosympathectomised male mongrel dogs were prepared to measure blood pressure, heart rate and external carotid blood flow. The thyroid artery was cannulated for infusions of agonists. In 16 of these dogs, a spinal cannula was inserted (C1-C3) for infusions of 5-HT.
  
  
  RESULTS
  The external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine remained unaffected after intracarotid or i.v. fluoxetine. In contrast, the vasodilator responses to capsaicin, but not those to α-CGRP or acetylcholine, were inhibited after chronic oral treatment with fluoxetine (300 µg/kg; for 90 days) or intrathecal 5-HT.
  
  
  CONCLUSIONS
  Chronic oral fluoxetine inhibited capsaicin-induced external carotid vasodilatation, and this inhibition could partly explain its potential prophylactic antimigraine action.
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, México.
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Muñoz-Islas
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, México.
authors.forename: Abimael
authors.initials: A
authors.lastname: González-Hernández
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, México.
authors.forename: Jair
authors.initials: J
authors.lastname: Lozano-Cuenca
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, México.
authors.forename: Martha Beatríz
authors.initials: MB
authors.lastname: Ramírez-Rosas
authors.affiliation: Departamento de Investigación y Posgrado, Escuela Superior de Medicina del I.P.N., México.
authors.forename: Roberto
authors.initials: R
authors.lastname: Medina-Santillán
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, México.
authors.forename: David
authors.initials: D
authors.lastname: Centurión
authors.affiliation: Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus Medical Center, The Netherlands.
authors.forename: Antoinette
authors.initials: A
authors.lastname: MaassenVanDenBrink
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, México cvillalon@cinvestav.mx.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Villalón
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002211:Capsaicin / Q000008:administration & dosage*; D002343:Carotid Artery, Internal / Q000187:drug effects* / Q000502:physiology*; D004285:Dogs; D004347:Drug Interactions; D005473:Fluoxetine / Q000008:administration & dosage*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D002211:Capsaicin; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors; D014665:Vasodilator Agents
keywords: 5-HT; Capsaicin; fluoxetine; migraine; vasodilatation; α-CGRP