Corticostriatal plasticity, neuronal ensembles, and regulation of drug-seeking behavior

Prog Brain Res. 2017:235:93-112. doi: 10.1016/bs.pbr.2017.07.013. Epub 2017 Oct 12.


The idea that interconnected neuronal ensembles code for specific behaviors has been around for decades; however, recent technical improvements allow studying these networks and their causal role in initiating and maintaining behavior. In particular, the role of ensembles in drug-seeking behaviors in the context of addiction is being actively investigated. Concurrent with breakthroughs in quantifying ensembles, research has identified a role for synaptic glutamate spillover during relapse. In particular, the transient relapse-associated changes in glutamatergic synapses on accumbens neurons, as well as in adjacent astroglia and extracellular matrix, are key elements of the synaptic plasticity encoded by drug use and the metaplasticity induced by drug-associated cues that precipitate drug-seeking behaviors. Here, we briefly review the recent discoveries related to ensembles in the addiction field and then endeavor to link these discoveries with drug-induced striatal plasticity and cue-induced metaplasticity toward deeper neurobiological understandings of drug seeking.

Keywords: Cocaine self-administration; Cued reinstatement; Glutamate; Neuronal ensembles; Nucleus accumbens; Spines; Synaptic plasticity; Synaptic potentiation.

Publication types

  • Review

MeSH terms

  • Anesthetics, Local / administration & dosage
  • Animals
  • Cerebral Cortex / cytology*
  • Cerebral Cortex / drug effects
  • Cocaine / administration & dosage
  • Corpus Striatum / cytology*
  • Corpus Striatum / drug effects
  • Drug-Seeking Behavior / physiology*
  • Humans
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Neurons / physiology*


  • Anesthetics, Local
  • Cocaine