Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter.
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.
Giros
B
B
Howard Hughes Medical Institute Laboratories, Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Jaber
M
M
Jones
S R
SR
Wightman
R M
RM
Caron
M G
MG
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D004399:Dynorphins / Q000235:genetics; D004745:Enkephalins / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D018390:Gene Targeting; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D011498:Protein Precursors / Q000235:genetics; D051381:Rats
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D004745:Enkephalins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D004399:Dynorphins; C033660:preproenkephalin; D000661:Amphetamine; D003042:Cocaine; D004298:Dopamine