An additional drug-induced synaptic adaptation in the NAc occurs during protracted (6–7 weeks) withdrawal from cocaine self-administration, a period that is associated with an increase in cue-induced cocaine seeking (a model for craving) (Grimm et al., 2001). While normally synapses on NAc MSNs contain the AMPAR subunit GluA2, rendering AMPARs Ca-impermeable, 6 weeks following cessation of cocaine self-administration, a proportion of synaptic AMPARs now lack GluA2 making them Ca-permeable (Conrad et al., 2008). As discussed below, this change in the stoichiometry of AMPARs has important behavioral ramifications.
