Voltammetric assessment of dopamine clearance in the absence of the dopamine transporter: no contribution of other transporters in core or shell of nucleus accumbens.
Cocaine elevates dopamine (DA) in the nucleus accumbens (NAc) by blocking the uptake of DA through the DA transporter (DAT). It is commonly believed that the reinforcing properties of cocaine depend upon interaction with the DAT, however, cocaine is still reinforcing in mice with a genetic deletion of the DAT (DAT-KO mice). Although cocaine continues being able to elevate DA in the NAc of these mice, this mechanism is unclear. The present voltammetric study in brain slices was designed to examine the role of the norepinephrine and serotonin transporters in removing DA from the extracellular space in the NAc of DAT-KO mice. We found no effects of any monoamine uptake inhibitors, including cocaine (10 microM), desipramine (10 microM) or fluoxetine (10 microM) on the clearance of DA in these mice. Therefore, it appears that there is no compensatory uptake of DA by alternative transporters either in core or shell of the nucleus accumbens of DAT-KO mice.
Mateo
Yolanda
Y
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA.
Budygin
Evgeny A
EA
John
Carrie E
CE
Banks
Matthew L
ML
Jones
Sara R
SR
D000818:Animals; D001681:Biological Assay; D003042:Cocaine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D005473:Fluoxetine / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017551:Microdialysis; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters / Q000378:metabolism*
D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493228:Slc6a2 protein, mouse; C493215:Slc6a3 protein, mouse; C493231:Slc6a4 protein, mouse; D027981:Symporters; D005473:Fluoxetine; D003042:Cocaine; D003891:Desipramine; D004298:Dopamine