Dopamine transporter synthesis and degradation rate in rat striatum and nucleus accumbens using RTI-76.
Intracerebroventricular injections of the irreversible dopamine transporter (DAT) inhibitor, RTI-76 [3beta-(3-p-chlorophenyl) tropan-2beta-carboxylic acid p-isothiocyanatophenylethyl ester hydrochloride], decreased DAT binding in both the striatum and nucleus accumbens as measured by both [3H]GBR12935 and by [3H]WIN35,428. This decrease was dose-related, with 100 nmol RTI-76 producing approximately a 50% decrease in both regions. The maximal inhibition of DAT binding was observed 24 h after RTI-76 injection, and binding was fully restored 7 days after injection. The DAT protein half-life determined under these conditions was about 2 days. [3H]Nisoxetine binding at norepinephrine transporters in the cortex was not altered by RTI-76 administration at any time point or dose examined.
Kimmel
H L
HL
Yerkes Regional Primate Research Center, Emory University, Atlanta, GA 30329, USA. hlkimme@emory.edu
Carroll
F I
FI
Kuhar
M J
MJ
D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D003042:Cocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000494:pharmacology; D007276:Injections, Intraventricular; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009638:Norepinephrine / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters; D014326:Tropanes / Q000494:pharmacology*
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010879:Piperazines; C101790:RTI 76; C493226:Slc6a2 protein, rat; C493216:Slc6a3 protein, rat; D027981:Symporters; D014326:Tropanes; D005473:Fluoxetine; C011386:nisoxetine; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine; D003042:Cocaine; D004298:Dopamine; D009638:Norepinephrine