On a behavioural level, the infusion of astrocyte-conditioned media into the rodent NAcc incites locomotor sensitization and reward processing with methamphetamines (Narita et al. 2005, 2006b). The evidence, therefore, suggests that glial-mediated dysfunction, especially in glutamatergic neurotransmission, leads to adverse behavioural sequelae associated with initiation, maintenance, and relapse to cocaine and other psychostimulants. In short, cocaine alters the ability to maintain extracellular levels of glutamate and decreases synaptic plasticity in the NAcc. This renders both mice and humans more susceptible to cue-induced reinstatement. Drugs that increase xCT and/or EAAT2/GLT-1 expression restore extracellular glutamate levels, thus preventing reinstatement.
