MK-801 reinstates drug-seeking behaviour in cocaine-trained rats

Neuroreport. 1998 Mar 9;9(4):637-40. doi: 10.1097/00001756-199803090-00014.


We evaluated the incentive motivational properties of MK-801 by determining its priming effect on drug-seeking behaviour following extinction of cocaine self-administration, an animal model for drug craving. Rats were allowed to self-administrate cocaine (0.5 mg/kg) or saline during 10 daily sessions. MK-801 (0.1-0.25 mg/kg, i.p.) dose-dependently reinstated responding for cocaine following an extinction period of 3 weeks. Responding was selectively enhanced in the previously drug-paired hole and was completely absent in rats with a history of saline self-administration. These data provide evidence for a possible role of NMDA receptors in the incentive motivation underlying cocaine-seeking behaviour. In addition, the ability of MK-801 to elicit drug-seeking behaviour may prove to be a serious drawback for the proposed use of NMDA antagonists in the treatment of drug addiction.

MeSH terms

  • Analysis of Variance
  • Animals
  • Cocaine / administration & dosage*
  • Dizocilpine Maleate / pharmacology*
  • Dose-Response Relationship, Drug
  • Extinction, Psychological
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Self Administration*
  • Substance-Related Disorders / physiopathology*


  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate
  • Cocaine