Silent Synapse-Based Circuitry Remodeling in Drug Addiction

Exposure to cocaine, and likely other drugs of abuse, generates alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor silent glutamatergic synapses in the nucleus accumbens. These immature synaptic contacts evolve after drug withdrawal to redefine the neurocircuital properties. These results raise at least three critical questions: (1) what are the molecular and cellular mechanisms that mediate drug-induced generation of silent synapses; (2) how are neurocircuits remodeled upon generation and evolution of drug-generated silent synapses; and (3) what behavioral consequences are produced by silent synapse-based circuitry remodeling? This short review analyzes related experimental results, and extends them to some speculations.