Effects of long-term cigarette smoking on the human locus coeruleus

Violetta Klimek, Meng Yang Zhu, Ginny Dilley, Lisa Konick, James C. Overholser, Herbert Y. Meltzer, Warren L. May, Craig A. Stockmeier, Gregory A. Ordway*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


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 α2-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 α2-adrenoceptors were measured. Results: Amounts of tyrosine hydroxylase immunoreactivity and radioligand binding to α2-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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)821-827
Number of pages7
JournalArchives of general psychiatry
Issue number9
StatePublished - 2001

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Psychiatry and Mental health


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