title: Elevated agonist binding to alpha2-adrenoceptors in the locus coeruleus in major depression.
abstract: BACKGROUND
  Recent postmortem studies demonstrate disrupted neurochemistry of the noradrenergic locus coeruleus (LC) in major depression (MD). Increased levels of tyrosine hydroxylase and decreased levels of norepinephrine transporter implicate a norepinephrine deficiency in the LC in MD. Here we describe a study of alpha2-adrenoceptors in the LC and raphe nuclei of subjects with MD compared with psychiatrically normal control subjects.
  
  
  METHODS
  The specific binding of p-[125I]iodoclonidine to alpha2-adrenoceptors was measured at multiple levels along the rostrocaudal extent of the LC in postmortem tissue from 14 control and 14 MD subjects. In addition, p-[125I]iodoclonidine binding was measured in the dorsal and median raphe nuclei in the same tissue sections.
  
  
  RESULTS
  The specific binding of p-[125I]iodoclonidine to alpha2-adrenoceptors was significantly elevated throughout the LC from MD compared with matched control subjects. No significant differences were observed in p-[125I]iodoclonidine binding to alpha2-adrenoceptors in the raphe nuclei comparing MD and control subjects.
  
  
  CONCLUSIONS
  Given that alpha2-adrenoceptors are upregulated in laboratory animals by treatment with drugs that deplete norepinephrine, our findings implicate a premortem deficiency of brain norepinephrine in the region of the locus coeruleus in subjects with MD.
authors.affiliation: Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Ordway
authors.forename: Jane
authors.initials: J
authors.lastname: Schenk
authors.forename: Craig A
authors.initials: CA
authors.lastname: Stockmeier
authors.forename: Warren
authors.initials: W
authors.lastname: May
authors.forename: Violetta
authors.initials: V
authors.lastname: Klimek
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000378:metabolism*; D000328:Adult; D000345:Affinity Labels; D000368:Aged; D001344:Autopsy; D001345:Autoradiography; D003000:Clonidine / Q000031:analogs & derivatives*; D003865:Major Depressive Disorder / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008125:Locus Coeruleus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019275:Radiopharmaceuticals; D011903:Raphe Nuclei / Q000378:metabolism / Q000473:pathology; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000345:Affinity Labels; D019275:Radiopharmaceuticals; D018341:Receptors, Adrenergic, alpha-2; C053113:4-iodoclonidine; D003000:Clonidine