Mice lacking the norepinephrine transporter
are supersensitive to psychostimulants
by
Xu F, Gainetdinov RR, Wetsel WC, Jones SR,
Bohn LM, Miller GW, Wang YM, Caron MG
Howard Hughes Medical Institute Laboratories,
Departments of Cell Biology and Medicine,
Duke University Medical Center,
Durham, North Carolina 27710, USA.
Nat Neurosci 2000 May; 3(5):465-71

ABSTRACT

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.

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