title: Effects of orally administered Augmentin on glutamate transporter 1, cystine-glutamate exchanger expression and ethanol intake in alcohol-preferring rats.
abstract: Alcohol dependence is associated with deficits in glutamate uptake and impairment of glutamate homeostasis in different brain reward regions. Glutamate transporter subtype 1 (GLT-1), cystine-glutamate exchanger (xCT) and glutamate/aspartate transporter (GLAST) are one of the key players in regulating extracellular glutamate concentration in the brain. Parenteral treatment with ceftriaxone, β-lactam antibiotic, has been reported to attenuate ethanol consumption and reinstatement to cocaine-seeking behavior, in part, by restoring the expression of GLT-1 and xCT in mesocorticolimbic brain regions in rats. In this study, we focused to test Augmentin (amoxicillin/clavulanate), which can be administered orally to subjects. Therefore, we examined the effects of orally administered Augmentin on ethanol intake as well as GLT-1, xCT and GLAST expression in male alcohol-preferring (P) rats. We found that orally administered Augmentin significantly attenuated ethanol consumption in P rats as compared to the vehicle-treated group. Importantly, the attenuation in ethanol consumption was associated with a significant upregulation of GLT-1 and xCT expression in nucleus accumbens (NAc) and prefrontal cortex (PFC). There was no effect of orally administered Augmentin on GLAST expression in either NAc or PFC. These findings present strong evidence that oral administration of Augmentin can be used as an alternative to parenteral treatment.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA.
authors.forename: Alqassem Y
authors.initials: AY
authors.lastname: Hakami
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA.
authors.forename: Fahad S
authors.initials: FS
authors.lastname: Alshehri
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA.
authors.forename: Yusuf S
authors.initials: YS
authors.lastname: Althobaiti
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA. Electronic address: youssef.sari@utoledo.edu.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Sari
mesh_terms: D000284:Administration, Oral; D000428:Alcohol Drinking / Q000188:drug therapy / Q000503:physiopathology*; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003553:Cystine / Q000378:metabolism; D004326:Drinking / Q000187:drug effects; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism*; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051381:Rats; D065093:beta-Lactamase Inhibitors / Q000008:administration & dosage*
chemical_list: D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; C493395:Slc1a2 protein, rat; D065093:beta-Lactamase Inhibitors; D003553:Cystine; D019980:Amoxicillin-Potassium Clavulanate Combination
keywords: Augmentin; Ethanol dependence; GLAST; GLT-1; Oral gavage; xCT