Cocaine experience controls bidirectional synaptic plasticity in the nucleus accumbens

J Neurosci. 2007 Jul 25;27(30):7921-8. doi: 10.1523/JNEUROSCI.1859-07.2007.


Plasticity of glutamatergic synapses is a fundamental mechanism through which experience changes neural function to impact future behavior. In animal models of addiction, glutamatergic signaling in the nucleus accumbens (NAc) exerts powerful control over drug-seeking behavior. However, little is known about whether, how or when experience with drugs may trigger synaptic plasticity in this key nucleus. Using whole-cell synaptic physiology in NAc brain slices, we demonstrate that a progression of bidirectional changes in glutamatergic synaptic strength occurs after repeated in vivo exposure to cocaine. During a protracted drug-free period, NAc neurons from cocaine-experienced mice develop a robust potentiation of AMPAR-mediated synaptic transmission. However, a single re-exposure to cocaine during extended withdrawal becomes a potent stimulus for synaptic depression, abruptly reversing the initial potentiation. These enduring modifications in AMPAR-mediated responses and plasticity may provide a neural substrate for disrupted processing of drug-related stimuli in drug-experienced individuals.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cocaine / administration & dosage*
  • Cocaine-Related Disorders* / physiopathology
  • Cocaine-Related Disorders* / psychology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Nerve Net / drug effects
  • Nerve Net / physiology
  • Neuronal Plasticity / drug effects*
  • Neuronal Plasticity / physiology
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / physiology
  • Synapses / drug effects*
  • Synapses / physiology


  • Cocaine