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.
De Vries
T J
TJ
Research Institute of Neurosciences Vrije Universiteit, Department of Pharmacology, Free University, Medical Facility, Amsterdam, The Netherlands.
Schoffelmeer
A N
AN
Binnekade
R
R
Mulder
A H
AH
Vanderschuren
L J
LJ
D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D012646:Self Administration; D019966:Substance-Related Disorders / Q000503:physiopathology*
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D003042:Cocaine