title: Effects of ampicillin on cystine/glutamate antiporter and glutamate transporter 1 isoforms as well as ethanol drinking in male P rats.
abstract: Evidence demonstrated that glial cells, mainly astrocytes, regulate glutamate uptake through 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. Cystine-glutamate antiporter (xCT) is another glial protein critical in regulating glutamate transmission. Several studies from our laboratory demonstrated that attenuation of ethanol intkae was associated in part with upregulation of xCT and GLT-1 expression suggesting the important role of these transporters in the treatment of ethanol dependence. We found recently that β-lactam antibiotic, ampicillin, 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 on the expression of xCT and GLT-1 isoforms (GLT-1a and GLT-1b) as well as on GLAST expression. We found that ampicillin reduced ethanol intake as compared to the saline (control)-treated group. In addition, we found that ampicillin induced upregulation of xCT, GLT-1a, and GLT-1b expression in both the PFC and NAc, but had no effect on GLAST expression. Our findings provide significant role of ampicillin on upregulating xCT and GLT-1 isoforms expression, might be suggested as possible targets for the attenuation of ethanol consumption.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Toledo, OH, USA.
authors.forename: Fawaz
authors.initials: F
authors.lastname: Alasmari
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Toledo, OH, USA.
authors.forename: Sawsan
authors.initials: S
authors.lastname: Abuhamdah
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Toledo, OH, USA. Electronic address: youssef.sari@utoledo.edu.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Sari
mesh_terms: D000428:Alcohol Drinking; D026922:Amino Acid Transport Systems, Acidic / Q000378:metabolism*; D000667:Ampicillin / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D027182:Amino Acid Transport System y+
chemical_list: D026922:Amino Acid Transport Systems, Acidic; D000667:Ampicillin; D000900:Anti-Bacterial Agents; D027342:Excitatory Amino Acid Transporter 2; D020033:Protein Isoforms; C000723960:Slc7a11 protein, rat; D027182:Amino Acid Transport System y+
keywords: Ampicillin; Ethanol intake; GLAST; GLT-1a; GLT-1b; Glutamate; xCT