• Walailuk Kerdsan, Samur Thanoi, and Sutisa Nudmamud-Thanoi.
• Department of Anatomy, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand.
• Basic Clin. Pharmacol. Toxicol. 2012 Oct 1;111(4):275-8.

AbstractMethamphetamine (METH), an addictive psychostimulant, can induce glutamate release in several brain areas such as cerebral cortex, hippocampus and striatum. Excess glutamate is ordinarily removed from the synaptic cleft by glutamate transporters for maintaining homoeostasis. EAAT3, a subtype of glutamate transporter expressed mainly by neurons, is a major glutamate transporter in the hippocampus and cortex. Therefore, this study examined the effects of acute and sub-acute METH administration on the expression of the EAAT3 in the hippocampal formation, striatum and frontal cortex. Male Sprague-Dawley rats received vehicle injections (i.p.) for 13 days followed by one injection of METH (8 mg/kg, i.p.) on day 14 in acute group. Animals received METH (4 mg/kg, i.p.) or vehicle for 14 days in sub-acute and control groups, respectively. EAAT3 immunoreactivity was determined by western blotting followed by measurement of the integrated optical density. A significant increase in EAAT3 was found in the hippocampal formation after sub-acute, but not acute, METH administration. Conversely, a significant decrease in EAAT3 in striatum was observed in both acute and sub-acute groups. A trend towards a decrease in EAAT3 was also found in frontal cortex in the sub-acute group. Our results of decreased EAAT3 in striatum and frontal cortex suggest deficits of cortico-striatal glutamatergic synapses after METH exposure. Increased EAAT3 expression in the hippocampus may be a compensatory response to possible deficits of glutamatergic neurotransmission induced by METH. Moreover, our findings provide further support for glutamatergic dysfunction with abnormalities involving a transporter important in the regulation of neuronal glutamate.© 2012 The Authors Basic & Clinical Pharmacology & Toxicology © 2012 Nordic Pharmacological Society.

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