Towards an Understanding of Integrative Brain Functions

Re-evaluation of the role of the dopamine transporter in dopamine system homeostatis

Raul R. Gainetdinov ^a,1, Sara R. Jones ^a, Fabio Fumagalli ^a,2, R. Mark Wightman ^b, Marc G. Caron ^a,*
^a Howard Hughes Medical Institute Laboratories, Department of Cell Biology and Medicine, Duke University Medical Center, Durham, NC 27710 USA, ^b Department of Chemistry and Curriculum in Neurobiology, University of North Carolina, Chapel Hill, NC 27599 USA

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Abstract
Mice with a genetic deletion of the dopamine transporter (DAT) were used to asses its role in the function of dopamine (DA) neurons. Profound alterations in the homeostasis of the nigrostriatal DA system were induced by the absence of the DAT. Extracellular levels of DA were elevated and clearance of released DA was 300-times slower than in control mice. This was accompanied by a 20-fold decrease in tissue DA levels and a paradoxical doubling of the rate of DA synthesis. A crucial role is indicated for the DAT in maintenance of DA neuron presynaptic function, particularly in the control of storage mechanisms.

*Corresponding author: caron002@mc.duke.edu

1) Raul R. Gainetdinov is a visiting fellow from the Institute of Pharmacology, RAMS, Baltiyskaya 8, 125315, Moscow, Russia.

2) Fabio Fumagalli is a visiting fellow from the Center of Neuropharmacology, Institute of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy.

Brain Research Reviews 26 (1998) 148-153
Copyright © 1998 Elsevier Science B. V. All rights reserved.