Regulation of norepinephrine transporter abundance by catecholamines and desipramine in vivo

David Weinshenker, Sylvia S. White, Martin A. Javors, Richard D. Palmiter, Patricia Szot

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

The norepinephrine transporter (NET) regulates adrenoreceptor signaling by controlling the availability of synaptic norepinephrine (NE), and it is a direct target for some classes of antidepressant drugs. NET levels are normal in dopamine β-hydroxylase knockout (Dbh -/-) mice that lack NE, demonstrating that the NET does not require endogenous NE for appropriate regulation under physiological conditions. In contrast, tyrosine hydroxylase knockout (Th -/-) mice that lack both NE and dopamine (DA) have reduced levels of NET, suggesting that it is down-regulated by a complete absence of catecholamines and not NE per se. Chronic treatment with the NET inhibitor, desipramine (DMI), reduced NET levels in both control and Dbh -/- mice, demonstrating that NE is not required for the regulation of NET by antidepressant drugs. There are some qualitative and quantitative differences in the down-regulation of the NET by catecholamine depletion and DMI treatment, suggesting that different mechanisms may be involved.

Original languageEnglish (US)
Pages (from-to)239-246
Number of pages8
JournalBrain Research
Volume946
Issue number2
DOIs
StatePublished - Aug 16 2002

Keywords

  • Antidepressant
  • Desipramine
  • Dopamine β-hydroxylase
  • Knockout mouse
  • Nisoxetine
  • Norepinephrine transporter

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Fingerprint Dive into the research topics of 'Regulation of norepinephrine transporter abundance by catecholamines and desipramine in vivo'. Together they form a unique fingerprint.

Cite this