AMPA receptor plasticity in the nucleus accumbens after repeated exposure to cocaine

This review focuses on cocaine-induced postsynaptic plasticity in the nucleus accumbens (NAc) involving changes in AMPA receptor (AMPAR) transmission. First, fundamental properties of AMPAR in the NAc are reviewed. Then, we provide a detailed and critical analysis of literature demonstrating alterations in AMPAR transmission in association with behavioral sensitization to cocaine and cocaine self-administration. We conclude that cocaine exposure leads to changes in AMPAR transmission that depend on many factors including whether exposure is contingent or non-contingent, the duration of withdrawal, and whether extinction training has occurred. The relationship between changes in AMPAR transmission and responding to cocaine or cocaine-paired cues can also be affected by these variables. However, after prolonged withdrawal in the absence of extinction training, our findings and others lead us to propose that AMPAR transmission is enhanced, resulting in stronger responding to drug-paired cues. Finally, many results indicate that the state of synaptic transmission in the NAc after cocaine exposure is associated with impairment of AMPAR-dependent plasticity. This may contribute to a broad range of addiction-related behavioral changes.