Silent Synapse-Based Circuitry Remodeling in Drug Addiction

Int J Neuropsychopharmacol. 2016 Apr 29;19(5):pyv136. doi: 10.1093/ijnp/pyv136. Print 2016 May.

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.

Keywords: accumbens; anti-addictive; circuitry remodeling; cocaine; incubation; silent synapse.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptation, Physiological
  • Adaptation, Psychological
  • Animals
  • Behavior, Addictive / metabolism
  • Behavior, Addictive / physiopathology
  • Behavior, Addictive / psychology
  • Central Nervous System Stimulants / adverse effects*
  • Cocaine / adverse effects*
  • Cocaine-Related Disorders / metabolism
  • Cocaine-Related Disorders / physiopathology*
  • Cocaine-Related Disorders / psychology
  • Drug Users / psychology*
  • Excitatory Postsynaptic Potentials
  • Glutamic Acid / metabolism
  • Humans
  • Neuronal Plasticity / drug effects*
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Nucleus Accumbens / physiopathology
  • Receptors, Glutamate / drug effects*
  • Receptors, Glutamate / metabolism
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synaptic Transmission / drug effects*

Substances

  • Central Nervous System Stimulants
  • Receptors, Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype glutamate receptor, human
  • Glutamic Acid
  • Cocaine