Thus, protracted abstinence from cocaine self-administration can induce at least two separate alterations in glutamatergic function in the NAcb. As the period of abstinence proceeds, AMPAR-mediated responses are potentiated due to an increase in synaptic GluA2-lacking AMPARs. These GluA2-lacking AMPARs in the NAcb may be critical for the enduring drive to seek cocaine. The second effect of cocaine is its ability to alter the induction of synaptic plasticity. The persistent neuroadaptations that occur during abstinence from cocaine self-administration (Martin et al., 2006; Moussawi et al., 2009), especially the inability to produce further plastic changes, are an intriguing parallel to the inflexible responding of individuals repeatedly exposed to psychostimulants. Thus, AMPAR-selective pharmacotherapeutics could reduce the recidivistic and compulsive nature of cocaine and amphetamine addiction.
