Acute administration of the NMDA receptor antagonist, D-CPPene (SDZ EAA 494; 3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid; 2 mg/kg), abolished (P < 0.01) the sensitised mesoaccumbens dopamine response to nicotine (0.4 mg/kg) measured using in vivo microdialysis, but not the increased locomotor activity, observed in rats pretreated with nicotine prior to the test day. D-CPPene enhanced (P < 0.01) the mesoaccumbens dopamine response, but not the locomotor response, to acute nicotine given to drug-naive rats. The data suggest that sensitised mesoaccumbens dopamine responses to nicotine involve co-stimulation of NMDA receptors but that this effect is not closely related to sensitisation of the locomotor response to the drug.