Abstract
The aim of this study was to examine the role of metabotropic glutamate receptor 5 (mGluR5) in the toxic action of methamphetamine on dopaminergic neurones in rats. Methamphetamine (10 mg/kg sc), administered five times, reduced the levels of dopamine and its metabolites in striatal tissue when measured 72 h after the last injection. A selective antagonist of mGluR5, 2-methyl-6-(phenylethynyl)pyridine (MPEP; 5 mg/kg ip), when administered five times immediately before each methamphetamine injection reversed the above-mentioned methamphetamine effects. A single MPEP (5 mg/kg ip) injection reduced the basal extracellular dopamine level in the striatum, as well as dopamine release stimulated either by methamphetamine (10 mg/kg sc) or by intrastriatally administered veratridine (100 μM). Moreover, it transiently diminished the methamphetamine (10 mg/kg sc)-induced hyperthermia and reduced basal body temperature. MPEP administered into the striatum at high concentrations (500 μM) increased extracellular dopamine levels, while lower concentrations (50–100 μM) were devoid of any effect. The results of this study suggest that the blockade of mGluR5 by MPEP may protect dopaminergic neurones against methamphetamine-induced toxicity. Neuroprotection rendered by MPEP may be associated with the reduction of the methamphetamine-induced dopamine efflux in the striatum due to the blockade of extrastriatal mGluR5, and with a decrease in hyperthermia.
Published Version
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