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Role of Glutamate Transporters in Alcohol and Methamphetamine Co-Abuse

Alshehri, Fahad

Abstract Details

2015, Master of Science, University of Toledo, Pharmaceutical Science.
Alcohol and methamphetamine are one of the most widespread drugs of abuse. Recently, studies are focusing on the association between drugs of abuse and glutamatergic system. It has been found that both alcohol and methamphetamine can disturb glutamate transport, release, and clearance. Alternatively, ceftriaxone, known to upregulate one of the major glutamate transporters glutamate transporter 1 (GLT-1), showed a promising effect against cocaine seeking, methamphetamine reinstatement in conditioned place preference, and alcohol consumption. These effects are suggested to be associated in part with upregulation of GLT-1 expression levels in central reward brain regions leading to normalization of extracellular glutamate concentrations in these regions. However, there is little known about co-abuse of alcohol and methamphetamine. Therefore, this study examined the effects of ceftriaxone on alcohol and methamphetamine co-abuse in both striatum and hippocampus of Wistar rats. Wistar rats were gavaged with ethanol 6 g/kg for seven days and injected intraperitoneally with methamphetamine 10 mg/kg, four times with two hours apart. Furthermore, studies have shown the hyperglutamatergic state with drug uses, including methamphetamine and alcohol. We suggest here that this hyperglutamatergic state might be associated with a deficit in glutamate transport. Thus, we tested ceftriaxone to prevent downregulation of GLT-1 induced by administration of both alcohol and methamphetamine. Three ceftriaxone injections were given after the administration of high doses of methamphetamine. As a result, administration of alcohol and methamphetamine caused a significant downregulation of GLT-1 expression levels as compared to control naive groups in both striatum and hippocampus. Conversely, both xCT and GLAST expression levels remained unaffected as compared to naive control group. Ceftriaxone treatment normalized the level of GLT-1 expression levels in both striatum and hippocampus. These findings show the important role of GLT-1 in alcohol and methamphetamine co-abuse. Therefore, GLT-1 could be considered as a target for future treatment against neurotoxicity induced by administration of alcohol and methamphetamine.
Youssef Sari (Committee Chair)
Wissam Aboulalaiwi (Committee Member)
Zahoor Shah (Committee Member)
65 p.

Recommended Citations

Citations

  • Alshehri, F. (2015). Role of Glutamate Transporters in Alcohol and Methamphetamine Co-Abuse [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1433195506

    APA Style (7th edition)

  • Alshehri, Fahad. Role of Glutamate Transporters in Alcohol and Methamphetamine Co-Abuse. 2015. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=toledo1433195506.

    MLA Style (8th edition)

  • Alshehri, Fahad. "Role of Glutamate Transporters in Alcohol and Methamphetamine Co-Abuse." Master's thesis, University of Toledo, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1433195506

    Chicago Manual of Style (17th edition)