Cocaine, reward, movement and monoamine transporters.
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 However, previously-held views that DAT blockade was the sole site for cocaine reward have been replaced by a richer picture of multitransporter involvement with the rewarding and aversive actions of cocaine.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.
Uhl
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GR
Molecular Neurobiology Branch, NIDA-IRP, NIH, Baltimore, MD 21224, USA. guhl@intra.nida.nih.gov
Hall
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Sora
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D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000235:genetics / Q000378:metabolism; D004298:Dopamine / Q000502:physiology; D050483:Dopamine Plasma Membrane Transport Proteins; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D008960:Models, Psychological; D009043:Motor Activity / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012201:Reward; D012701:Serotonin / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; C493214:SLC6A3 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C493228:Slc6a2 protein, mouse; C493215:Slc6a3 protein, mouse; C493231:Slc6a4 protein, mouse; D027981:Symporters; D012701:Serotonin; D003042:Cocaine; D004298:Dopamine; D009638:Norepinephrine