Amphetamine and methamphetamine reduce striatal dopamine transporter function without concurrent dopamine transporter relocalization

J Neurochem. 2012 Oct;123(2):288-97. doi: 10.1111/j.1471-4159.2012.07875.x. Epub 2012 Aug 23.


Amphetamine (AMPH) and methamphetamine (METH) alter dopamine transporter (DAT) function. In vitro heterologous cell line and synaptosome studies demonstrate AMPH-induced DAT internalization, implicating relocalization in reduced DAT uptake following drug exposure. However, few studies have evaluated DAT localization following in vivo AMPH/METH administration. To determine DAT subcellular localization following drug administration, a centrifugation technique was developed to isolate striatal synaptosomal membrane and vesicle fractions. DAT was distributed between the synaptosomal membrane (60%) and endosomal vesicles (40%), and in vitro application of the protein kinase C activator phorbol 12-myristate 13-acetate to striatal synaptosomes caused DAT internalization into the vesicle fractions. In contrast, neither single nor repeated in vivo AMPH and/or METH administrations altered DAT localization 5, 15, 30, or 60 min post-treatment, despite reduced DAT uptake. Importantly, repeated METH injections uniformly decreased total DAT immunoreactivity within all fractions 7 days post-treatment. These findings suggest that factors other than internalization can contribute to the observed acute and persistent DAT dysfunction and dopaminergic deficits following in vivo AMPH or METH administration.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amphetamine / pharmacology*
  • Animals
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Corpus Striatum / physiology*
  • Dopamine Plasma Membrane Transport Proteins / antagonists & inhibitors*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Dopamine Plasma Membrane Transport Proteins / physiology*
  • Male
  • Methamphetamine / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Synaptosomes / drug effects
  • Synaptosomes / physiology


  • Dopamine Plasma Membrane Transport Proteins
  • Methamphetamine
  • Amphetamine