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.