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Amphetamine and methamphetamine reduce striatal dopamine transporter function without concurrent dopamine transporter relocalization
Author(s) -
German Christopher L.,
Hanson Glen R.,
Fleckenstein Annette E.
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2012.07875.x
Subject(s) - dopamine transporter , methamphetamine , dopaminergic , dopamine plasma membrane transport proteins , dopamine , amphetamine , internalization , pharmacology , meth , in vivo , chemistry , striatum , synaptosome , biology , endocrinology , in vitro , biochemistry , cell , microbiology and biotechnology , monomer , organic chemistry , acrylate , polymer
J. Neurochem. (2012) 123 , 288–297. Abstract 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.