In vivo labelling of the neuronal dopamine uptake complex in the mouse striatum by [3H]GBR 12783.
Various characteristics of the in vivo striatal binding of [3H]GBR 12783 (1-[2-(diphenylmethoxy)-ethyl]-4-(3-phenyl-1[3H]-2-propenyl)pipera zine), a specific ligand of the neuronal dopamine uptake complex, were determined in mice. Increasing doses of the ligand revealed the saturability of the binding at a single site with half-maximal saturation at a dose of approximately 7 mumol/kg and an apparent maximal number of binding sites (Bmax) of 12.8 pmol/mg protein in striatum. Specific binding was prevented by various dopamine uptake blockers, pyrovalerone, GBR 13069, GBR 12783, N-[1-2-benzo(b)thiophenyl)cyclohexyl] piperidine, cocaine, methylphenidate and was inhibited in a stereoselective manner by the enantiomers of nomifensine. Other drugs which are not dopamine uptake blockers either did not modify [3H]GBR 12783 binding (the diphenylbutylpiperazine derivative flupenthixol) or increased it (the diphenylpiperazine derivative flunarizine or the chemically unrelated compounds fenfluramine and SKF 525A). A close correlation was found between occupancy of the striatal [3H]GBR 12783 binding site and the stimulant locomotor effect of the drug. A similar specific striatal binding of [3H]GBR 12783 was evidenced in both NMRI and CD1 strains. It was concluded that [3H]GBR 12783 administered in vivo provides a measure of the density of dopamine uptake sites in mouse striatum.
Unité de Neuropsychopharmacologie Expérimentale, U.R.A. 1170 CNRS, Faculté de Médecine et Pharmacie de Rouen, Saint-Etienne du Rouvray, France.
J M
JM
Vaugeois
J J
JJ
Bonnet
J
J
Costentin
D000818:Animals; D001665:Binding Sites; D002531:Cerebellum / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins; D008774:Methylphenidate / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D011335:Proadifen / Q000494:pharmacology; D013997:Time Factors; D014316:Tritium
D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D014179:Neurotransmitter Uptake Inhibitors; D010879:Piperazines; D014316:Tritium; D008774:Methylphenidate; C039737:1-(2-(diphenylmethoxy)ethyl)-4-(3-phenyl-2-propenyl)piperazine; D011335:Proadifen; D004298:Dopamine