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

• Cefazolin and cefoperazone treatments decreased ethanol intake.
• Cefazolin and cefoperazone upregulated GLT-1a and GLT-1b in NAc and PFC.
• Cefazolin increased xCT expression in NAc and PFC.
• Cefoperazone upregulated xCT expression in NAc.

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.