R-(+)-HA-966, an antagonist for the glycine/NMDA receptor, prevents locomotor sensitization to repeated cocaine exposures.

Repeated administration of cocaine results in a reverse tolerance or sensitization to the locomotor stimulant properties of cocaine. In this study, we examined the effect of an antagonist for the strychinine-insensitive glycine receptor of the NMDA receptor complex, R-(+)-HA-966, on the development of locomotor sensitization to cocaine. Co-administration of R-(+)-HA-966 with repeated cocaine prevented locomotor sensitization to a subsequent challenge dose of cocaine. However, R-(+)-HA-966 (15 mg/kg i.p.) did not attenuate locomotor activation to an acute dose of cocaine (15 mg/kg). These results indicate that the glycine/NMDA receptor is involved in locomotor sensitization to repeated cocaine administration but not in the locomotor activation to the acute stimulant effects of cocaine administration.