Cocaine experience controls bidirectional synaptic plasticity in the nucleus accumbens

Saïd Kourrich, Patrick E. Rothwell, Jason R. Klug, Mark J. Thomas

Research output: Contribution to journalArticlepeer-review

294 Scopus citations

Abstract

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 drugrelated stimuli in drug-experienced individuals.

Original languageEnglish (US)
Pages (from-to)7921-7928
Number of pages8
JournalJournal of Neuroscience
Volume27
Issue number30
DOIs
StatePublished - Jul 25 2007

Keywords

  • AMPAR
  • Addiction
  • Long-term depression
  • Metaplasticity
  • NMDAR
  • Psychostimulant
  • Synaptic scaling

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