Chronic exposure to cocaine results in a time–dependent and transient reorganization of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) and N-methyl-D-aspartate (NMDA) glutamate receptors at nucleus accumbens (NAc) medium spiny neuron (MSN) synapses, as well as structural changes in the spine head of NAc MSNs that correlate with distinct forms of synaptic plasticity. For example, chronic cocaine induces surface expression of NMDA receptors, silent synapse formation, and long-term depression (LTD) at early withdrawal time points. During more prolonged withdrawal, these synaptic changes reverse with the result being increased expression of surface AMPA receptors, a consolidation of the synapse into a mushroom-shaped spine, and long-term potentiation (LTP). These effects rapidly revert back again upon exposure to a challenge dose of cocaine leading to restructuring of the spine into thin spines and a depression of synaptic strength.