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Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter

Giros, Bruno, Jaber, Mohamed, Jones, Sara R., Wightman, R. Mark, Caron, Marc G.·1996·Nature

DOI 10.1038/379606a0

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Abstract

Disruption of the mouse dopamine transporter gene results in spontaneous hyperlocomotion despite major adaptive changes, such as decreases in neurotransmitter and receptor levels. In homozygote mice, dopamine persists at least 100 times longer in the extracellular space, explaining the biochemical basis of the hyperdopaminergic phenotype and demonstrating the critical role of the transporter in regulating neurotransmission. The dopamine transporter is an obligatory target of cocaine and amphetamine, as these psychostimulants have no effect on locomotor activity or dopamine release and uptake in mice lacking the transporter.

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Authors: Giros, B., Jaber, M., Jones, S. R., Wightman, R. M., & Caron, M. G.
Affiliations: Howard Hughes Medical Institute (US)
University of North Carolina at Chapel Hill (US)
ORCID: Jaber, Mohamed
Jones, Sara R.
Wightman, R. Mark
Caron, Marc G.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1996-02
Volume: 379
Issue: 6566
Pages: 606-612
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/379606a0
OpenAlex: W2014793858
Cited by: 2,476
References: 41
Citations by year: 2026: 34 · 2025: 39 · 2024: 32 · 2023: 61 · 2022: 52 · 2021: 62 · 2020: 47 · 2019: 54 · 2018: 62 · 2017: 67 · 2016: 58 · 2015: 74 · 2014: 93 · 2013: 73 · 2012: 97
FWCI: 43.87
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords: dopamine transporter, hyperlocomotion, cocaine, amphetamine, psychostimulants, dopamine, neurotransmitter levels, locomotor activity, dopamine release, dopamine uptake
MeSH terms: Amphetamine, Animals, Carrier Proteins, Cell Line, Cocaine, Dopamine, Dynorphins, Enkephalins, Female, Gene Expression Regulation, Locomotion, Male, Membrane Glycoproteins, Mice, Inbred C57BL, Nerve Tissue Proteins, Protein Precursors, Mice, Knockout, Gene Targeting, Membrane Transport Proteins, Dopamine Plasma Membrane Transport Proteins, Mice, Rats

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Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter

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