Cocaine-induced neuroadaptations in glutamate transmission: potential therapeutic targets for craving and addiction

Ann N Y Acad Sci. 2010 Feb:1187:35-75. doi: 10.1111/j.1749-6632.2009.05144.x.


A growing body of evidence indicates that repeated exposure to cocaine leads to profound changes in glutamate transmission in limbic nuclei, particularly the nucleus accumbens. This review focuses on preclinical studies of cocaine-induced behavioral plasticity, including behavioral sensitization, self-administration, and the reinstatement of cocaine seeking. Behavioral, pharmacological, neurochemical, electrophysiological, biochemical, and molecular biological changes associated with cocaine-induced plasticity in glutamate systems are reviewed. The ultimate goal of these lines of research is to identify novel targets for the development of therapies for cocaine craving and addiction. Therefore, we also outline the progress and prospects of glutamate modulators for the treatment of cocaine addiction.

Publication types

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

MeSH terms

  • Adaptation, Physiological / drug effects
  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Cocaine / toxicity*
  • Cocaine-Related Disorders / drug therapy
  • Cocaine-Related Disorders / physiopathology*
  • Cocaine-Related Disorders / psychology
  • Dopamine / physiology
  • Excitatory Amino Acid Agonists / therapeutic use
  • Excitatory Amino Acid Antagonists / therapeutic use
  • Glutamic Acid / physiology*
  • Humans
  • Models, Neurological
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / physiopathology
  • Rats
  • Receptors, Glutamate / classification
  • Receptors, Glutamate / drug effects
  • Receptors, Glutamate / physiology
  • Reinforcement, Psychology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Synaptic Transmission / drug effects*
  • Synaptic Transmission / physiology


  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Receptors, Glutamate
  • Glutamic Acid
  • Cocaine
  • Dopamine