From: scerir (scerir@libero.it)
Date: Mon Apr 23 2001 - 05:14:43 MDT
The Journal of Neuroscience, 2001, 21:RC141:1-4
(RAPID COMMUNICATION)
"Cocaine and Amphetamine Increase Extracellular Dopamine in the Nucleus
Accumbens of Mice Lacking the Dopamine Transporter Gene"
Ezio Carboni (1), Cécile Spielewoy (2), Cinzia Vacca (1), Marika
Nosten-Bertrand (2), Bruno Giros (2), and Gaetano Di Chiara (1)
(1) Department of Toxicology and Consiglio Nazionale delle Ricerche Center
for Neuropharmacology, University of Cagliari, 09126 Cagliari, Italy.
(2) Neurobiology and Psychiatry Faculté de Medicine de Creteil,
94000 Creteil, France
Behavioral and biochemical studies suggest that dopamine (DA) plays a role
in the reinforcing and addictive properties of drugs of abuse.
Recently, this hypothesis has been challenged on the basis of the
observation that, in mice genetically lacking the plasma membrane dopamine
transporter [DAT-knock out (DAT-KO)], cocaine maintained its reinforcing
properties of being self-administered and inducing place preference, despite
the failure to increase extracellular dopamine in the dorsal striatum.
Here we report that, in DAT-KO mice, cocaine and amphetamine increase
dialysate dopamine in the medial part of the *nucleus accumbens*. Moreover,
reboxetine, a specific blocker of the noradrenaline transporter, increased
DA in the nucleus accumbens of DAT-KO but not of wild-type mice; in
contrast, GBR 12909, a specific blocker of the dopamine transporter,
increased dialysate dopamine in the *nucleus accumbens* of wild-type but not
of DAT-KO mice.
These observations provide an explanation for the persistence of cocaine
reinforcement in DAT-KO mice and support the hypothesis of a primary role of
*nucleus accumbens* dopamine in drug reinforcement.
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