title: Effects of cefazolin and cefoperazone on glutamate transporter 1 isoforms and cystine/glutamate exchanger as well as alcohol drinking behavior in male alcohol-preferring rats.
abstract: Previously, we have reported that cefazolin and cefoperazone treatments attenuated ethanol consumption, at least in part, through upregulation of GLT-1 expression in male alcohol-preferring (P) rats. In this study, we determined the effects of these compounds on the expression of GLT-1 isoforms (GLT-1a and GLT-1b), cysteine/glutamate exchanger (xCT), which is another glial glutamate transporter co-localized with GLT-1, and glutamate/aspartate transporter (GLAST). We found that cefazolin and cefoperazone treatments decreased ethanol intake and upregulated both GLT-1 isoforms, GLT-1a and GLT-1b, in nucleus accumbens (NAc) and prefrontal cortex (PFC) compared to saline treated group. In addition, cefazolin increased the expression of xCT in NAc and PFC, while cefoperazone upregulated xCT expression only in NAc. However, we did not find any significant differences in GLAST expression between the treated and control groups. Overall, our findings suggest that cefazolin and cefoperazone may be considered as potential compounds for the treatment of ethanol dependence.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA.
authors.forename: Fawaz
authors.initials: F
authors.lastname: Alasmari
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA.
authors.forename: P S S
authors.initials: PSS
authors.lastname: Rao
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: D000428:Alcohol Drinking; D026922:Amino Acid Transport Systems, Acidic / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D002437:Cefazolin / Q000008:administration & dosage*; D002438:Cefoperazone / Q000008:administration & dosage*; D000431:Ethanol / Q000008:administration & dosage; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism*; 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; D015854:Up-Regulation; D027182:Amino Acid Transport System y+
chemical_list: D026922:Amino Acid Transport Systems, Acidic; D000900:Anti-Bacterial Agents; D002437:Cefazolin; D002438:Cefoperazone; D000431:Ethanol; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D020033:Protein Isoforms; C493395:Slc1a2 protein, rat; C493392:Slc1a3 protein, rat; C000723960:Slc7a11 protein, rat; D027182:Amino Acid Transport System y+
keywords: Alcohol intake; GLAST; GLT-1a; GLT-1b; Glutamate; xCT