Dopamine transporter synthesis and degradation rate in rat striatum and nucleus accumbens using RTI-76

Neuropharmacology. 2000 Feb 14;39(4):578-85. doi: 10.1016/s0028-3908(99)00160-4.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / metabolism*
  • Cocaine / analogs & derivatives
  • Cocaine / pharmacology
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Uptake Inhibitors / pharmacology
  • Fluoxetine / analogs & derivatives
  • Fluoxetine / pharmacology
  • Injections, Intraventricular
  • Ligands
  • Male
  • Membrane Glycoproteins*
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins*
  • Norepinephrine / metabolism
  • Norepinephrine Plasma Membrane Transport Proteins
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Piperazines / pharmacology
  • Protein Binding
  • Rats
  • Rats, Sprague-Dawley
  • Symporters*
  • Tropanes / pharmacology*

Substances

  • Carrier Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Uptake Inhibitors
  • Ligands
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Norepinephrine Plasma Membrane Transport Proteins
  • Piperazines
  • RTI 76
  • Slc6a2 protein, rat
  • Slc6a3 protein, rat
  • Symporters
  • Tropanes
  • Fluoxetine
  • nisoxetine
  • (1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester
  • 1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine
  • Cocaine
  • Dopamine
  • Norepinephrine