Reduced levels of norepinephrine transporters in the locus coeruleus in major depression

Violetta Klimek, Craig Stockmeier, James Overholser, Herbert Y Meltzer, Sheila Kalka, Ginny Dilley, Gregory A. Ordway*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

314 Scopus citations


The norepinephrine transporter (NET) is a membrane protein responsible for termination of the action of synaptic norepinephrine and is a site of action of many drugs used to treat major depression. The present study determined whether the binding of [3H]nisoxetine to the NET is altered in the locus coeruleus (LC) in major depression, using brain tissue collected postmortem from subjects diagnosed with major depression and from age- matched normal control subjects. Thirteen of the 15 major depressive subjects studied died by suicide. The distribution of [3H]nisoxetine binding along the rostro-caudal axis of the nucleus was uneven and was paralleled by a similar uneven distribution of neuromelanin-containing cells in both major depressives and psychiatrically normal control subjects. The binding of [3H] nisoxetine to NETs in the midcaudal portion of the LC from major depressive subjects was significantly lower than that from age-matched, normal control subjects. The binding of [3H]nisoxetine to NETs in other regions of the LC was similar in major depressives and control subjects. In contrast to reductions in binding to NETs, there were no significant differences in the number of noradrenergic cells at any particular level of the LC between major depressives and normal control subjects. The decreased binding of [3H]nisoxetine to NETs in the LC in major depression may reflect a compensatory downregulation of this transporter protein in response to an insufficient availability of its substrate (norepinephrine) at the synapse.

Original languageEnglish (US)
Pages (from-to)8451-8458
Number of pages8
JournalJournal of Neuroscience
Issue number21
StatePublished - 1997


  • Locus coeruleus
  • Major depression
  • Noradrenergic
  • Norepinephrine
  • Norepinephrine transporters
  • Norepinephrine uptake
  • Suicide
  • Tricyclic antidepressants

ASJC Scopus subject areas

  • Neuroscience(all)

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