hyperpolarization of rat hippocampal neurons (Mulholland et al. 2009). In addition, the pharmacological inhibition or genetic deletion of equilibrative nucleoside transporter, a transmembrane glycoprotein responsible for nucleotide reuptake (Griffiths et al. 1997), increases alcohol consumption by decreasing the expression of EAAT2/GLT-1 and aquaporin, a channel involved in regulating brain water homeostasis, blood flow, glucose transport and metabolism, blood-brain barrier integrity, glutamate turnover, and syn-aptic plasticity (Lee et al. 2013). The cephalosporin antibiotic ceftriaxone not only restores expression of these transporters but also curtails drinking, which suggests crosstalk between adenosine and glutamate (Lee et al. 2013). As a potential genetic underpinning, a silent G→A mutation in exon 5 of EAAT2/ GLT-1 increases vulnerability to alcohol dependence and impulsivity (Foley et al. 2004; Sander et al. 2000). In addition to EAAT2/GLT-1, the other major astrocyte-expressed EAAT (EAAT1/GLAST) also affects alcohol consumption. In mice, a circadian period gene (Per2Brdm1) deletion decreases EAAT1/GLAST expression and increases alcohol consumption; similarly, acamprosate reduces glutamate levels and decreases alcohol intake (Spanagel et al. 2005). Human Per2 single nucleotide polymorphisms are also associated with increased alcohol consumption and may also be associated with sleep problems in alcoholism (Comasco et al. 2010).
