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 (3 beta-(3-p-chlorophenyl) tropan-2 beta-carboxylic acid p-isothiocyanatophenylethyl ester hydrochloride), decreased DAT binding in both the striatum and nucleus accumbens as measured by both [H-3]GBR12935 and by [H-3]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. [H-3]Nisoxetine binding at norepinephrine transporters in the cortex was not altered by RTI-76 administration at any time point or dose examined. (C) 2000 Elsevier Science Ltd. All rights reserved.