Dissociable effects of antagonism of NMDA and AMPA/KA receptors in the nucleus accumbens core and shell on cocaine-seeking behavior

Neuropsychopharmacology. 2001 Sep;25(3):341-60. doi: 10.1016/S0893-133X(01)00235-4.


The purpose of the present experiment was to investigate the involvement of NMDA and AMPA/KA receptors in the nucleus accumbens core and shell in the control over cocaine-seeking behavior by drug-associated cues. Rats were trained under a second-order schedule of reinforcement for cocaine with five infusions of cocaine being available in each daily session. The NMDA receptor antagonist AP-5 and the AMPA/KA receptor antagonist LY293558 were infused directly into the core or shell. LY293558 infused into the core produced a dose-dependent decrease in responding during both the first, cocaine-unaffected interval and also after cocaine had been self-administered in subsequent intervals. By contrast, AP-5 infused into the core had no effect on responding. Infusion of AP-5 into the shell had the limited effect of decreasing responding during the second interval only. There were no effects of LY293558 infused into the shell. These results indicate that NMDA and AMPA receptor-mediated glutamate transmission in the core and shell are dissociably involved in cocaine-seeking behavior controlled in part by drug-associated cues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / administration & dosage
  • 2-Amino-5-phosphonovalerate / pharmacology
  • Animals
  • Cocaine-Related Disorders / psychology*
  • Conditioning, Operant / drug effects
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Extinction, Psychological / drug effects
  • Isoquinolines / administration & dosage
  • Isoquinolines / pharmacology
  • Male
  • Microinjections
  • Nucleus Accumbens / anatomy & histology
  • Nucleus Accumbens / drug effects*
  • Rats
  • Receptors, AMPA / antagonists & inhibitors*
  • Receptors, Kainic Acid / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Reinforcement Schedule
  • Self Administration
  • Tetrazoles / administration & dosage
  • Tetrazoles / pharmacology


  • Excitatory Amino Acid Antagonists
  • Gluk1 kainate receptor
  • Isoquinolines
  • Receptors, AMPA
  • Receptors, Kainic Acid
  • Receptors, N-Methyl-D-Aspartate
  • Tetrazoles
  • tezampanel
  • 2-Amino-5-phosphonovalerate