Differential control over cocaine-seeking behavior by nucleus accumbens core and shell

Nat Neurosci. 2004 Apr;7(4):389-97. doi: 10.1038/nn1217. Epub 2004 Mar 21.


Nucleus accumbens (NAc) dopamine is widely implicated in mediating the reinforcing effects of drugs of abuse. However, the precise function of the NAc itself in drug self-administration has been difficult to establish. Here we show a neural double-dissociation of the behavioral processes that underlie cocaine self-administration in rats. Whereas selective excitotoxic lesions of the NAc core had only a minor effect on the acquisition of responding for cocaine under a standard schedule of continuous reinforcement, these lesions profoundly impaired the acquisition of drug-seeking behavior that was maintained by drug-associated conditioned reinforcers and assessed using a second-order schedule of cocaine reinforcement. In contrast, selective excitotoxic lesions of the NAc shell did not impair drug self-administration or the acquisition of cocaine-seeking, but they did attenuate the psychostimulant effects of cocaine. These results further our understanding of how the NAc controls drug-seeking and drug-taking behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Appetitive Behavior / drug effects
  • Appetitive Behavior / physiology*
  • Association Learning / physiology
  • Cocaine / administration & dosage*
  • Cocaine-Related Disorders / physiopathology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Male
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / physiology*
  • Rats
  • Rats, Inbred Strains
  • Reinforcement, Psychology*
  • Self Administration


  • Cocaine