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Effects of Beta-Lactam Antibiotics on Cystine /Glutamate Exchanger Transporter and Glutamate Transporter 1 Isoforms as well as Ethanol Drinking Behavior in Male P Rats

Alasmari, Fawaz Fayez
http://rave.ohiolink.edu/etdc/view?acc_num=mco1435826676

Abstract Details

2015, Master of Science (MS), University of Toledo, Pharmaceutical Sciences (Pharmacology/Toxicology).
Evidence demonstrated that glial cells, mainly astrocytes, regulate glutamate uptake, which is regulated by several glutamate transporters. Among these glutamate transporters, glutamate transporter 1 (GLT-1, its human homolog is excitatory amino acid transporter-2) is responsible for the majority of glutamate uptake by glial cells. Cystine-glutamate antiporter (xCT) is another glial protein that regulates glutamate transmission. It has been previously shown that a ß-lactam antibiotic, ceftriaxone, upregulated GLT-1 and xCT expression levels in prefrontal cortex (PFC) and nucleus accumbens (NAc), and consequently reduced ethanol intake and relapse-like ethanol intake in alcohol-preferring (P) rats. It has been shown that found recently that ß-lactam antibiotics (ampicillin, cefazolin, and cefoperazone) upregulated GLT-1 expression in the prefrontal cortex (PFC) and nucleus accumbens (NAc) and consequently reduced ethanol intake in alcohol-preferring (P) rats. In this study, we investigated the effects of ampicillin, cefazolin, and cefoperazone on the expression levels of xCT and GLT-1 isofroms (GLT-1a and GLT-1b) as well as on GLAST expression using western blot assay. We found that these compounds reduced alcohol intake as compared to saline treated group. In addition, we found that ampicillin, cefazolin and cefoperazone induced upregulation of GLT-1a and GLT-1b expression levels in both PFC and NAc, but no significant effects in glutamate/aspartate transporter, GLAST, expression were induced. We also found that ampicillin and cefazolin increased xCT expression in both NAc and PFC. However, cefoperazone increased xCT expression only in the NAc. Additionally, we found that cefoperazone prevented relapse like-ethanol intake. Our findings provide additional information about the potential uses of ß-lactam antibiotics as target drugs for the treatment of alcohol dependence.
Youssef Sari, Dr./PhD (Advisor)
Ezdihar Hassoun, Dr./PhD (Committee Member)
Zahoor Shah, Dr./PhD (Committee Member)
80 p.
Pharmacology; Toxicology

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Citations

  • Alasmari, F. F. (2015). Effects of Beta-Lactam Antibiotics on Cystine /Glutamate Exchanger Transporter and Glutamate Transporter 1 Isoforms as well as Ethanol Drinking Behavior in Male P Rats [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1435826676

    APA Style (7th edition)

  • Alasmari, Fawaz. Effects of Beta-Lactam Antibiotics on Cystine /Glutamate Exchanger Transporter and Glutamate Transporter 1 Isoforms as well as Ethanol Drinking Behavior in Male P Rats. 2015. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1435826676.

    MLA Style (8th edition)

  • Alasmari, Fawaz. "Effects of Beta-Lactam Antibiotics on Cystine /Glutamate Exchanger Transporter and Glutamate Transporter 1 Isoforms as well as Ethanol Drinking Behavior in Male P Rats." Master's thesis, University of Toledo, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=mco1435826676

    Chicago Manual of Style (17th edition)

mco1435826676
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This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.