Interaction of [3H]GBR 12935 and GBR 12909 with the dopamine uptake complex in nucleus accumbens.
Although some behavioral effects of cocaine are hypothesized to be due to blockade of dopamine uptake in nucleus accumbens, it has been reported that in nucleus accumbens there are no specific cocaine binding sites and that cocaine is a weak inhibitor of dopamine uptake. [3H]GBR 12935 and an unlabelled analog, GBR 12909, are ligands that bind with great affinity and specificity to a site on dopamine uptake complex in striatum. We therefore investigated the interaction of these GBR compounds with the dopamine uptake complex in nucleus accumbens. We found specific high affinity [3H]GBR 12935 binding and a significant correlation between displacement of [3H]GBR 12935 binding by a series of compounds in striatum and nucleus accumbens. GBR 12909 inhibited dopamine uptake with equal potency in nucleus accumbens and striatum. Thus, there appear to be some aspects of the dopamine uptake complex in nucleus accumbens and striatum that are similar.
Berger
P
P
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510.
Elsworth
J D
JD
Arroyo
J
J
Roth
R H
RH
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D003042:Cocaine / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D014179:Neurotransmitter Uptake Inhibitors; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012686:Septal Nuclei / Q000378:metabolism*
D050483:Dopamine Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D014179:Neurotransmitter Uptake Inhibitors; D010879:Piperazines; C043425:vanoxerine; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine; D003042:Cocaine; D004298:Dopamine