title: Disruption of subcellular Arc/Arg 3.1 mRNA expression in striatal efferent neurons following partial monoamine loss induced by methamphetamine.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Barker-Haliski
authors.forename: Katharina
authors.initials: K
authors.lastname: Oldenburger
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Keefe
mesh_terms: D000818:Animals; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D004298:Dopamine / Q000378:metabolism*; D005786:Gene Expression Regulation; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009476:Neurons, Efferent / Q000187:drug effects / Q000378:metabolism*; D020258:Neurotoxicity Syndromes / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000697:Central Nervous System Stimulants; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C092069:activity regulated cytoskeletal-associated protein; D008694:Methamphetamine; D004298:Dopamine