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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amphetamine / pharmacology*
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Animals
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Carrier Proteins / drug effects
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Line
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Cocaine / pharmacology*
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Dopamine / metabolism*
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Dopamine Plasma Membrane Transport Proteins
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Dynorphins / genetics
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Enkephalins / genetics
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Female
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Gene Expression Regulation
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Gene Targeting
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Locomotion / drug effects
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Male
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Membrane Glycoproteins*
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Membrane Transport Proteins*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Nerve Tissue Proteins*
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Protein Precursors / genetics
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Rats
Substances
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Carrier Proteins
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Dopamine Plasma Membrane Transport Proteins
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Enkephalins
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Membrane Glycoproteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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Protein Precursors
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Dynorphins
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preproenkephalin
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Amphetamine
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Cocaine
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Dopamine