Next, alcohol induces glutamatergic neurotransmission abnormalities in astrocytes. Under physiological conditions, synaptic glutamate is removed by specific astrocyte transporters. The astrocytic excitatory amino acid transporter (EAAT)2 [glial glutamate transporter (GLT-1) in rodents] reuptakes glutamate from the extracellular space where it is intracellularly converted to glutamine for synaptic recycling (Niciu et al. 2012). Excessive extrasynaptic glutamate receptor stimulation initiates apoptosis, and the physiological activity of EAAT2/GLT-1 reduces excitotoxicity from synaptic spillover (Hardingham et al. 2010). In a rodent model of alcoholism, alcohol upregulates EAAT2/GLT-1 (Wu et al. 2011). EAAT2/GLT-1 is also upregulated in the amygdala and cingulate cortex of alcohol-dependent rats, and exposure-induced (but not spontaneously-induced) alcohol use can be antagonized with acamprosate, a glutamatergic neuromodulator (Rimondini et al. 2002; Hoffman et al. 2003). Although its expression is increased, alcohol disrupts EAAT2/ GLT-1-mediated functions, e.g., the modulation of potassium channel (Kv2.1)-dependent 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
