Abstract
Recent evidence enriches our understanding of the molecular sites of action of cocaine reward and locomotor stimulation. Dopamine transporter blockade by cocaine appears a sufficient explanation for cocaine-induced locomotion. Variation in DAT appears to cause differences in locomotion without drug stimulation. However, previously-held views that DAT blockade was the sole site for cocaine reward have been replaced by a richer picture of multitransporter involvement with the rewarding and aversive actions of cocaine. These new insights, derived from studies of knockout mice with simultaneous deletions and/or blockade of multiple transporters, provide a novel model for the rewarding action of this heavily-abused substance and implicate multiple monoamine systems in cocaine's hedonic activities.
Publication types
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Animals
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Brain / drug effects
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Brain / pathology
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Carrier Proteins / antagonists & inhibitors
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Carrier Proteins / genetics
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Carrier Proteins / physiology
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Cocaine / pharmacology*
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Cocaine-Related Disorders / genetics
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Cocaine-Related Disorders / metabolism
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Dopamine / physiology
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Dopamine Plasma Membrane Transport Proteins
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Genetic Predisposition to Disease
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Genetic Variation
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Humans
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Membrane Glycoproteins / antagonists & inhibitors
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology
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Membrane Transport Modulators
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Membrane Transport Proteins / antagonists & inhibitors
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Membrane Transport Proteins / deficiency
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Membrane Transport Proteins / genetics
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Membrane Transport Proteins / physiology*
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Mice
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Mice, Knockout
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Models, Neurological
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Models, Psychological
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Motor Activity / drug effects*
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Nerve Tissue Proteins / antagonists & inhibitors
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Nerve Tissue Proteins / deficiency
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / physiology*
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Norepinephrine / physiology
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Norepinephrine Plasma Membrane Transport Proteins
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Reward*
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Serotonin / physiology
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Serotonin Plasma Membrane Transport Proteins
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Symporters / antagonists & inhibitors
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Symporters / deficiency
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Symporters / genetics
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Symporters / physiology
Substances
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Carrier Proteins
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Dopamine Plasma Membrane Transport Proteins
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Membrane Glycoproteins
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Membrane Transport Modulators
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Membrane Transport Proteins
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Nerve Tissue Proteins
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Norepinephrine Plasma Membrane Transport Proteins
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SLC6A2 protein, human
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SLC6A3 protein, human
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SLC6A4 protein, human
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Serotonin Plasma Membrane Transport Proteins
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Slc6a2 protein, mouse
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Slc6a3 protein, mouse
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Slc6a4 protein, mouse
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Symporters
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Serotonin
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Cocaine
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Dopamine
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Norepinephrine