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Cocaine and amphetamine increase extracellular dopamine in the nucleus accumbens of mice lacking the dopamine transporter gene.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2001 May 01; Vol. 21 (9), pp. RC141: 1-4. - Publication Year :
- 2001
-
Abstract
- 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.
- Subjects :
- Adrenergic Uptake Inhibitors pharmacology
Animals
Carrier Proteins antagonists & inhibitors
Carrier Proteins genetics
Chromatography, High Pressure Liquid
Cocaine-Related Disorders etiology
Cocaine-Related Disorders metabolism
Dopamine Plasma Membrane Transport Proteins
Dopamine Uptake Inhibitors pharmacology
Extracellular Space chemistry
Extracellular Space metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Microdialysis
Morpholines pharmacology
Nucleus Accumbens metabolism
Piperazines pharmacology
Reboxetine
Reinforcement, Psychology
Amphetamine pharmacology
Carrier Proteins metabolism
Cocaine pharmacology
Dopamine metabolism
Membrane Glycoproteins
Membrane Transport Proteins
Nerve Tissue Proteins
Nucleus Accumbens drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 21
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 11312315