Current research has shown that manipulation at the glycine site of the NMDA receptor by various compounds can modulate NMDA receptor function and its behavioural consequences. The present study was conducted in order to neuroanatomically localize the effects of (+)-HA966 upon the acute and chronic effects of cocaine. Locomotor activity of Sprague-Dawley rats pretreated with (+)-HA966 (60 micrograms) into the nucleus accumbens five min prior to receiving cocaine (20 mg/kg i.p.) was significantly less than locomotor activity of the vehicle pretreated rats. Repeated treatment with cocaine resulted in sensitization to the locomotor stimulant effects of cocaine. Co-administration of (+)-HA966 with cocaine prevented the sensitization to a subsequent cocaine challenge, in which activity was comparable to levels of naive individuals given an acute injection of cocaine. These results suggest that the glycine site on NMDA receptors in the nucleus accumbens plays an important role in both the acute and sensitized responses to cocaine on locomotor activity.