title: Increased α2- and β1-adrenoceptor densities in postmortem brain of subjects with depression: differential effect of antidepressant treatment.
abstract: BACKGROUND
  Brain α2- and β-adrenoceptor alterations have been suggested in suicide and major depressive disorder.
  
  
  METHODS
  The densities of α2-, β1- and β2-adrenoceptors in postmortem prefrontal cortex of 26 subjects with depression were compared with those of age-, gender- and postmortem delay-matched controls. The effect of antidepressant treatment on α2- and β-adrenoceptor densities was also evaluated. α2- and β-adrenoceptor densities were measured by saturation experiments with respective radioligands [(3)H]UK14304 and [(3)H]CGP12177. β1- and β2-adrenoceptor subtype densities were dissected by means of β1-adrenoceptor selective antagonist CGP20712A.
  
  
  RESULTS
  Both, α2- and β1-adrenoceptors densities were higher in antidepressant-free depressed subjects (n=14) than those in matched controls (Δ~24%, p=0.013 and Δ~20%, p=0.044, respectively). In antidepressant-treated subjects (n=12), α2-adrenoceptor density remained increased over that in controls (Δ~20%), suggesting a resistance of α2-adrenoceptors to the down-regulatory effect of antidepressants. By contrast, β1-adrenoceptor density in antidepressant-treated depressed subjects was not different from controls, suggesting a possible down-regulation by antidepressants. The down-regulation of β1-adrenoceptor density in antidepressant-treated depressed subjects differs from the unaltered β1-adrenoceptor density observed in citalopram-treated rats and in a group of non-depressed subjects also treated with antidepressants (n=6). β2-adrenoceptor density was not altered in depressed subjects independently of treatment.
  
  
  CONCLUSIONS
  Antidepressant-treated subjects had been treated with a heterogeneous variety of antidepressant drugs. The results should be understood in the context of suicide victims with depression.
  
  
  CONCLUSIONS
  These results show the up-regulation of brain α2- and β1-adrenoceptors in depression and suggest that the regulation induced by chronic antidepressant treatment would be altered in these subjects.
authors.affiliation: Department of Pharmacology, University of the Basque Country (UPV/EHU), Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain. Electronic address: guadalupe.rivero@ehu.es.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Rivero
authors.affiliation: Department of Pharmacology, University of the Basque Country (UPV/EHU), Spain; BioCruces Health Research Institute, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
authors.forename: Ane M
authors.initials: AM
authors.lastname: Gabilondo
authors.affiliation: Laboratory of Neuropharmacology, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), University of the Balearic Islands, Spain.
authors.forename: Jesús A
authors.initials: JA
authors.lastname: García-Sevilla
authors.affiliation: Centre Universitaire Romand de Médicine Légale-site Genève, University of Geneva, Switzerland.
authors.forename: Romano
authors.initials: R
authors.lastname: La Harpe
authors.affiliation: Department of Pharmacology, University of the Basque Country (UPV/EHU), Spain; BioCruces Health Research Institute, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Callado
authors.affiliation: Department of Pharmacology, University of the Basque Country (UPV/EHU), Spain; BioCruces Health Research Institute, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
authors.forename: J Javier
authors.initials: JJ
authors.lastname: Meana
mesh_terms: D000328:Adult; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy / Q000473:pathology*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000032:analysis / Q000187:drug effects*; D018342:Receptors, Adrenergic, beta-1 / Q000032:analysis / Q000187:drug effects*; D012016:Reference Values; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000928:Antidepressive Agents; D018341:Receptors, Adrenergic, alpha-2; D018342:Receptors, Adrenergic, beta-1
keywords: Antidepressant drugs; Major depressive disorder; Postmortem human brain; Suicide; α(2)-adrenoceptors; β-adrenoceptors