in astrocytes (using dihydrokainic acid infusion into the lateral ventricle) reduces binge drinking (Smith et al., 2014), and GLAST KO mice show reduced voluntary ethanol consumption and do not exhibit CPP to ethanol (Karlsson et al., 2012). Alcohol-induced changes in adenosine signaling also contribute to disruptions in glutamate homeostasis in astrocytes (see (Lindberg et al., 2018) for review). Ethanol inhibits type 1 equilibrative nucleoside transporter (ENT1), which leads to elevated extracellular levels of adenosine and reduces GLT-1 expression (Matos et al., 2015). ENT1 KO mice show down-regulated GLT-1, reduced ethanol intoxication, and enhanced ethanol drinking (Choi et al., 2004; Lee et al., 2013). Restoring GLT-1 expression with the anti-inflammatory antibiotic ceftriaxone decreases ethanol self-administration, relapse-like drinking, and ethanol withdrawal severity in rats (Abulseoud et al., 2014; Das et al., 2015; Qrunfleh et al., 2013; Sari et al., 2011, 2016). N-acetylcysteine, the antioxidant precursor to glutathione, also enhances GLT-1 and xCT expression and reduces ethanol-reinforced responding, ethanol seeking, and reacquisition of seeking after ethanol abstinence in Long Evans rats (Lebourgeois et al., 2018). Unlike ceftriaxone, N-acetylcysteine does not affect cue-primed reinstatement of ethanol seeking in Sprague-Dawley rats, suggesting mechanisms other than modulating glutamate uptake contribute to these behaviors (Weiland et al.,
