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Disruption of subcellular Arc/Arg 3.1 mRNA expression in striatal efferent neurons following partial monoamine loss induced by methamphetamine
Author(s) -
BarkerHaliski Melissa L.,
Oldenburger Katharina,
Keefe Kristen A.
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/jnc.12017
Subject(s) - arc (geometry) , meth , neurotoxicity , striatum , monoamine neurotransmitter , biology , methamphetamine , immediate early gene , neuroscience , neuron , endocrinology , microbiology and biotechnology , medicine , gene expression , chemistry , dopamine , pharmacology , gene , biochemistry , toxicity , serotonin , receptor , mathematics , monomer , polymer , geometry , organic chemistry , acrylate
The immediate‐early gene Arc (activity‐regulated cytoskeleton‐associated protein) is provocative in the context of neuroplasticity because of its experience‐dependent regulation and mRNA transport to and translation at activated synapses. Normal rats have more preproenkephalin ‐negative ( ppe‐ neg; presumed striatonigral) neurons with cytoplasmic Arc mRNA than ppe‐ positive ( ppe ‐pos; striatopallidal) neurons, despite equivalent numbers of these neurons showing novelty‐induced transcriptional activation of Arc . Furthermore, rats with partial monoamine loss induced by methamphetamine ( METH ) show impaired Arc mRNA expression in both ppe ‐neg and ppe‐ pos neurons relative to normal animals following response‐reversal learning. In this study, Arc expression induced by exposure to a novel environment was used to assess transcriptional activation and cytoplasmic localization of Arc mRNA in striatal efferent neuron subpopulations subsequent to METH ‐induced neurotoxicity. Partial monoamine depletion significantly altered Arc expression. Specifically, basal Arc expression was elevated, but novelty‐induced transcriptional activation was abolished. Without novelty‐induced Arc transcription, METH ‐pre‐treated rats also had fewer neurons with cytoplasmic Arc mRNA expression, with the effect being greater for ppe‐ neg neurons. Thus, METH ‐induced neurotoxicity substantially alters striatal efferent neuron function at the level of Arc transcription, suggesting a long‐term shift in basal ganglia neuroplasticity processes subsequent to METH ‐induced neurotoxicity. Such changes potentially underlie striatally based learning deficits associated with METH ‐induced neurotoxicity.