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Title: Disruption of striatal glutamatergic/GABAergic homeostasis following acute methamphetamine in mice
Authors: Pereira, Frederico 
Cunha-Oliveira, Teresa 
Viana, Sofia 
Travassos, Ana Sofia 
Nunes, Sara 
Silva, Carlos 
Prediger, Rui 
Rego, Ana Cristina 
Ali, Syed 
Fontes Ribeiro, Carlos Alberto 
Issue Date: Sep-2012
Publisher: Neurotoxicology and Teratology
Serial title, monograph or event: Neurotoxicology and Teratology
Volume: 34
Abstract: Methamphetamine leads to functional changes in basal ganglia that are linked to impairment in motor activity. Previous studies from our group and others have shown that a single high-methamphetamine injection induces striatal dopaminergic changes in rodents. However, striatal glutamatergic, GABAergic and serotoninergic changes remain elusive under this methamphetamine regimen. Moreover, nothing is known about the participation of the receptor for advanced glycation end-products (RAGE), which is overexpressed upon synaptic dysfunction and glial response, on methamphetamine-induced striatal dysfunction. The aim of this work was to provide an integrative characterization of the striatal changes in amino acids, monoamines and astroglia, as well as in the RAGE levels, and the associated motor activity profile of C57BL/6 adult mice, 72 h after a single-high dose of methamphetamine (30 mg/kg, i.p.). Our findings indicate, for the first time, that methamphetamine decreases striatal glutamine, glutamate and GABA levels, as well as glutamine/glutamate and GABA/glutamate ratios, while serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels remain unchanged. This methamphetamine regimen also produced dopaminergic terminal degeneration in the striatum, as evidenced by dopamine and tyrosine hydroxylase depletion. Consistently, methamphetamine decreased the locomotor activity of mice, in the open field test. In addition, increased levels of glutamine synthase and glial fibrillary acidic protein were observed. Nevertheless, methamphetamine failed to change RAGE levels. Our results show that acute methamphetamine intoxication induces pronounced changes in the striatal glutamatergic/GABAergic and dopaminergic homeostasis, along with astrocyte activation. These neurochemical and glial alterations are accompanied by impairment in locomotor activity.
DOI: 10.1016/
Rights: closedAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais

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