Norepinephrine transporter knockout-induced up-regulation of brain alpha2A/C-adrenergic receptors.

Published

Journal Article

The norepinephrine transporter (NET) is responsible for the rapid removal of norepinephrine released from sympathetic neurons; this release is controlled by inhibitory alpha(2)-adrenergic receptors (alpha(2)ARs). Long-term inhibition of the NET by antidepressants has been reported to change the density and function of pre- and postsynaptic ARs, which may contribute to the antidepressant effects of NET inhibitors such as desipramine. NET-deficient (NET-KO) mice have been described to behave like antidepressant-treated mice. By means of quantitative real-time PCR we show that mRNAs encoding the alpha(2A)-adrenergic receptor (alpha(2A)AR) and the alpha(2C)-adrenergic receptor (alpha(2C)AR) are up-regulated in the brainstem, and that alpha(2C)AR mRNA is also elevated in the hippocampus and striatum of NET-KO mice. These results were confirmed at the protein level by quantitative autoradiography. The NET-KO mice showed enhanced binding of the selective alpha(2)AR antagonist [(3)H]RX821002 in several brain regions. Most robust increases (20-25%) in alpha(2)AR expression were observed in the hippocampus and in the striatum. Significant increases (16%) were also seen in the extended amygdala and thalamic structures. In an 'in vivo' test, the alpha(2)AR agonist clonidine (0.1 mg/kg) caused a significantly greater reduction of locomotor activity in NET-KO mice than in wild-type mice, showing the relevance of our findings at the functional level.

Full Text

Duke Authors

Cited Authors

  • Gilsbach, R; Faron-Górecka, A; Rogóz, Z; Brüss, M; Caron, MG; Dziedzicka-Wasylewska, M; Bönisch, H

Published Date

  • February 2006

Published In

Volume / Issue

  • 96 / 4

Start / End Page

  • 1111 - 1120

PubMed ID

  • 16417582

Pubmed Central ID

  • 16417582

International Standard Serial Number (ISSN)

  • 0022-3042

Digital Object Identifier (DOI)

  • 10.1111/j.1471-4159.2005.03598.x

Language

  • eng

Conference Location

  • England