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Amoxicillin and Augmentin Reduce Ethanol Intake and Increase GLT1 Expression as well as AKT Phosphorylation in Mesocorticolimbic Regions

Goodwani, Sunil G

Abstract Details

2014, Master of Science (MS), University of Toledo, College of Pharmacy.
Pharmacological upregulation of glutamate transporter 1 (GLT1), a principal mediator of glutamate reuptake, in mesocorticolimbic regions of the brain is associated with reduced drug and ethanol self-administration. It has been shown that administration of the beta-lactam antibiotic, ceftriaxone (CEF) attenuated ethanol and cocaine seeking behaviors as well as prevented ethanol-induced downregulation of GLT1 levels in central reward brain regions. However, it is not known if these effects are compound-specific. Therefore, the present study examined the effects of two other beta-lactam antibiotics, amoxicillin (AMOX) and Amoxicillin/Clavulanate (Augmentin, AUG), on ethanol drinking, as well as GLT1 and phosphorylated-AKT (pAKT) expression levels in the nucleus accumbens (Acb) and prefrontal cortex (PFC) of alcohol-preferring (P) rats. P rats were exposed to free-choice of ethanol (15% and 30%) for five weeks and were given five consecutive daily i.p. injections of saline vehicle, 100 mg/kg AMOX or 100 mg/kg AUG. Both compounds significantly decreased ethanol intake and significantly increased GLT1 expression in the Acb. AUG also increased GLT1 expression in the PFC. Results for changes in pAKT levels matched those for GLT1, indicating that beta-lactam antibiotic-induced reductions in ethanol intake are negatively associated with increases in GLT1 and pAKT levels within two critical brains regions mediating drug reward and reinforcement. These findings add to a growing literature that pharmacological increases in GLT1 expression are associated with decreases in ethanol, as well as drug, intake and suggest that one mechanism mediating this effect may be increased phosphorylation of AKT. Thus, GLT1 may serve as molecular targets for the treatment of alcohol and drug abuse.
Youssef Sari (Advisor)
Ezdihar Hassoun (Committee Member)
Surya Nauli (Committee Member)
Zahoor Shah (Committee Member)
51 p.

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Citations

  • Goodwani, S. G. (2014). Amoxicillin and Augmentin Reduce Ethanol Intake and Increase GLT1 Expression as well as AKT Phosphorylation in Mesocorticolimbic Regions [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1403873055

    APA Style (7th edition)

  • Goodwani, Sunil. Amoxicillin and Augmentin Reduce Ethanol Intake and Increase GLT1 Expression as well as AKT Phosphorylation in Mesocorticolimbic Regions. 2014. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1403873055.

    MLA Style (8th edition)

  • Goodwani, Sunil. "Amoxicillin and Augmentin Reduce Ethanol Intake and Increase GLT1 Expression as well as AKT Phosphorylation in Mesocorticolimbic Regions." Master's thesis, University of Toledo, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=mco1403873055

    Chicago Manual of Style (17th edition)