Mice lacking the norepinephrine transporter are supersensitive to psychostimulants.

Journal Article

The action of norepinephrine (NE) is terminated, in part, by its uptake into presynaptic noradrenergic neurons by the plasma-membrane NE transporter (NET), which is a target for antidepressants and psychostimulants. Disruption of the NET gene in mice prolonged the clearance of NE and elevated extracellular levels of this catecholamine. In a classical test for antidepressant drugs, the NET-deficient (NET-/-) animals behaved like antidepressant-treated wild-type mice. Mutants were hyper-responsive to locomotor stimulation by cocaine or amphetamine. These responses were accompanied by dopamine D2/D3 receptor supersensitivity. Thus altering NET expression significantly modulates midbrain dopaminergic function, an effect that may be an important component of the actions of antidepressants and psychostimulants.

Full Text

Duke Authors

Cited Authors

  • Xu, F; Gainetdinov, RR; Wetsel, WC; Jones, SR; Bohn, LM; Miller, GW; Wang, YM; Caron, MG

Published Date

  • May 2000

Published In

Volume / Issue

  • 3 / 5

Start / End Page

  • 465 - 471

PubMed ID

  • 10769386

International Standard Serial Number (ISSN)

  • 1097-6256

Digital Object Identifier (DOI)

  • 10.1038/74839

Language

  • eng

Conference Location

  • United States