title: Effects of long-term cigarette smoking on the human locus coeruleus.
abstract: BACKGROUND
  It has been hypothesized that cigarette smoking among subjects with major depression is a form of self-medication. To explore a possible biological basis for this hypothesis, noradrenergic proteins in the locus coeruleus (LC) were measured in long-term cigarette smokers and in nonsmokers. The LC was studied because elevated amounts of alpha2-adrenoceptors and tyrosine hydroxylase have been observed postmortem in the LCs of subjects with major depression or who commit suicide, and because long-term administration of antidepressant drugs to rats down-regulates these proteins in the LC.
  
  
  METHODS
  Postmortem LCs were obtained from long-term cigarette smokers (n=7) and from nonsmokers (n = 9), all of whom lacked diagnoses of major depression. Amounts of tyrosine hydroxylase immunoreactivity and radioligand binding to the norepinephrine transporter, monoamine oxidase A, and alpha2-adrenoceptors were measured.
  
  
  RESULTS
  Amounts of tyrosine hydroxylase immunoreactivity and radioligand binding to alpha2-adrenoceptors were significantly lower (approximately 60% and 40%, respectively) along the axis of the LCs of long-term smokers compared with nonsmokers. Smoking had no statistically significant effects on binding to monoamine oxidase A or to the norepinephrine transporter.
  
  
  CONCLUSIONS
  This is the first demonstration that cigarette smoking affects noradrenergic proteins in the LC. The direction of these changes is opposite to that observed when comparing subjects who have major depression with normal controls and the same as that produced by long-term antidepressant treatment in animals. If the present observations reflect long-term effects of smoking on premortem noradrenergic biochemistry, smoking-induced changes in LC biochemistry may strengthen the smoking habit among subjects with major depression.
authors.affiliation: Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216-4505, USA.
authors.forename: V
authors.initials: V
authors.lastname: Klimek
authors.forename: M Y
authors.initials: MY
authors.lastname: Zhu
authors.forename: G
authors.initials: G
authors.lastname: Dilley
authors.forename: L
authors.initials: L
authors.lastname: Konick
authors.forename: J C
authors.initials: JC
authors.lastname: Overholser
authors.forename: H Y
authors.initials: HY
authors.lastname: Meltzer
authors.forename: W L
authors.initials: WL
authors.lastname: May
authors.forename: C A
authors.initials: CA
authors.lastname: Stockmeier
authors.forename: G A
authors.initials: GA
authors.lastname: Ordway
mesh_terms: D000928:Antidepressive Agents / Q000494:pharmacology; D001345:Autoradiography; D015153:Blotting, Western; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology; D005260:Female; D006801:Humans; D008125:Locus Coeruleus / Q000737:chemistry* / Q000201:enzymology; D008297:Male; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012907:Smoking / Q000009:adverse effects* / Q000378:metabolism; D027981:Symporters; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D002352:Carrier Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; D027981:Symporters; D014446:Tyrosine 3-Monooxygenase