Measurements of extracellular glutamate levels in brain have generally shown increases produced by chronic EtOH exposure, especially after withdrawal or repeated cycles of withdrawal (Dahchour and De Witte 1999, 2003; Rossetti and Carboni 1995; Roberto et al. 2004b). These findings have generally been derived from measurements using in vivo microdialysis in brain. However, microdialysis measures of this type must be interpreted carefully, as both synaptic and nonsynaptic sources of glutamate contribute to the extracellular pool of this amino acid. Indeed, there is mounting evidence that changes in the cystine/glutamate exchanger generate increases in extracellular glutamate produced by some drugs of abuse (Kalivas 2009). Evidence of increased synaptic glutamate release has been observed in amygdala following chronic EtOH treatment (Lack et al. 2007; Zhu et al. 2007; Roberto et al. 2004b). Decreases in glutamate uptake have also been noted following chronic EtOH exposure (Melendez et al. 2005). There may be multiple factors that contribute to increased extracellular glutamate levels and increased glutamatergic transmission following chronic EtOH exposure and withdrawal.
