The Bermuda Triangle of cocaine-induced neuroadaptations

Trends Neurosci. 2010 Sep;33(9):391-8. doi: 10.1016/j.tins.2010.06.003. Epub 2010 Jul 23.


Activation of medium spiny neurons (MSNs) of the nucleus accumbens is critical for goal-directed behaviors including cocaine seeking. Studies in cocaine-experienced rodents have revealed three major categories of neuroadaptations that influence the ability of glutamate inputs to activate MSNs: changes in synaptic AMPA receptor levels, changes in extracellular non-synaptic glutamate levels and changes in MSN intrinsic membrane excitability. Most studies have focused on one of these adaptations. This review will consider the possibility that they are causally related and speculate about how time-dependent changes in their interactions may regulate MSN output during early and late withdrawal from repeated cocaine exposure.

Publication types

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

MeSH terms

  • Adaptation, Physiological*
  • Animals
  • Cocaine / pharmacology*
  • Glutamates / metabolism
  • Neurons / drug effects*
  • Neurons / metabolism
  • Nucleus Accumbens* / cytology
  • Nucleus Accumbens* / drug effects
  • Nucleus Accumbens* / metabolism
  • Receptors, AMPA / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism


  • Glutamates
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Cocaine