Effects of Administered Ethanol and Methamphetamine on Glial Glutamate Transporters in Rat Striatum and Hippocampus
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Exposure to ethanol (EtOH) or methamphetamine (MA) can lead to increase in extracellular glutamate concentration in the brain. Although studies from ours showed the effects of EtOH exposure on key glial glutamate transporters, little is known about the effects of sequential exposure to EtOH and MA or MA alone on certain glial glutamate transporters. In this study, we investigated the effects of sequential exposure to EtOH and MA on the expression of the major glutamate transporters, glutamate transporter 1 (GLT-1), as well as cystine/glutamate antiporter (xCT) and glutamate aspartate transporter (GLAST) in striatum and hippocampus. We also tested the effects of ceftriaxone (CEF), known to upregulate GLT-1, in animals administered EtOH and MA. Wistar rats were orally gavaged with EtOH (6 g/kg) or water for 7 days. On the following day (day 8), the rats received four intraperitoneal (i.p.) injections of MA (10 mg/kg) or saline (vehicle) occurring every 2 h. The rats were then treated with CEF (200 mg/kg/day, i.p.) or saline on days 8, 9, and 10. EtOH or MA exposure caused a significant downregulation of GLT-1 expression as compared to control groups in striatum and hippocampus. Furthermore, sequential exposure of EtOH and MA caused a significant downregulation of GLT-1 expression as compared to either drug administered alone in both brain regions. Importantly, GLT-1 expression was restored following CEF treatment. There were no significant differences on xCT and GLAST expression in striatum and hippocampus between all groups. These findings demonstrated that sequential exposure to EtOH and MA has additive effect in downregulation of GLT-1 and this effect can be attenuated by CEF treatment.
KeywordsGLT-1 Methamphetamine Ethanol Glutamate xCT GLAST Gavage
This work was supported in part by award number R01AA019458 (Y.S.) from the National Institutes on Alcohol Abuse and Alcoholism and also by start-up funds from the University of Toledo. The authors would like to thank Alqassem Hakami, Atiah Almalki, Fawaz Alasmari, and Sujan Das for their help in the experiments.
FSA participated in study design and conceptualization, drafted and revised the manuscript, and collected and analyzed the data. YSA collected the data and helped with the editing of manuscript. YS conceptualized and designed the study, critically revised the manuscript for intellectual content, and approved the final version of the manuscript.
Compliance with Ethical Standards
The experiments and housing procedures were approved by the Institutional Animal Care and Use committee at the University of Toledo with guidelines followed by the Institutional Animal Care and Use Committee of the National Institutes of Health and the Guide for the Care and Use of Laboratory.
Conflict of Interest
The authors declare that they have no conflict of interest.
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