title: Silent Synapse-Based Circuitry Remodeling in Drug Addiction.
abstract: Exposure to cocaine, and likely other drugs of abuse, generates α-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.
authors.affiliation: Department of Neuroscience, University of Pittsburgh, Pennsylvania (Dr Dong). yandong@pitt.edu.
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
mesh_terms: D000222:Adaptation, Physiological; D000223:Adaptation, Psychological; D000818:Animals; D016739:Behavior, Addictive / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D003042:Cocaine / Q000009:adverse effects*; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology; D055030:Drug Users / Q000523:psychology*; D019706:Excitatory Postsynaptic Potentials; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D009473:Neuronal Plasticity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D000697:Central Nervous System Stimulants; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C492973:alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype glutamate receptor, human; D018698:Glutamic Acid; D003042:Cocaine
keywords: accumbens; anti-addictive; circuitry remodeling; cocaine; incubation; silent synapse