title: Disruption of striatal glutamatergic/GABAergic homeostasis following acute methamphetamine in mice.
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.
authors.affiliation: Pharmacology and Experimental Therapeutics/Biomedical Institute for Research on Light and Image (IBILI), University of Coimbra, Portugal. fredcp@ci.uc.pt
authors.forename: Frederico C
authors.initials: FC
authors.lastname: Pereira
authors.forename: Teresa
authors.initials: T
authors.lastname: Cunha-Oliveira
authors.forename: Sofia D
authors.initials: SD
authors.lastname: Viana
authors.forename: Ana S
authors.initials: AS
authors.lastname: Travassos
authors.forename: Sara
authors.initials: S
authors.lastname: Nunes
authors.forename: Carlos
authors.initials: C
authors.lastname: Silva
authors.forename: Rui Daniel
authors.initials: RD
authors.lastname: Prediger
authors.forename: A Cristina
authors.initials: AC
authors.lastname: Rego
authors.forename: Syed F
authors.initials: SF
authors.lastname: Ali
authors.forename: Carlos Alberto Fontes
authors.initials: CA
authors.lastname: Ribeiro
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D017127:Glycation End Products, Advanced; D005973:Glutamine; D012701:Serotonin; D018698:Glutamic Acid; D008694:Methamphetamine; D006897:Hydroxyindoleacetic Acid; D005680:gamma-Aminobutyric Acid; D004298:Dopamine