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

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.