Cocaine self-administration can also alter regulation of glutamate release in the NAcb. Decreased basal extracellular glutamate concentration is observed in the NAcb in animals abstinent from cocaine self-administration (Baker et al., 2003; Kalivas and Hu, 2006; Pierce et al., 1996) due to impaired function of the glial cysteine-glutamate exchanger, which transports glial glutamate into the extracellular space. The amelioration of this deficit may, in part, explain the efficacy of glutamate transport modulators to decrease cocaine seeking (Knackstedt et al., 2009; Baker, et al., 2003; Martínez-Raga, et al., 2008). Decreased basal glutamate levels impair the ability for synapses to undergo LTP and/or LTD in glutamatergic transmission, and indeed, NAcb core neurons failed to express LTD or LTP in animals withdrawn or extinguished from voluntary cocaine self-administration, respectively (Martin et al., 2006; Moussawi et al., 2009).
