The NMDA receptor antagonist dizocilpine (MK-801) stereoselectively inhibits morphine-induced place preference conditioning in mice

The effect of the non-competitive NMDA receptor antagonist dizocilpine (MK-801) on conditioned place preference induced by morphine was studied in mice. As expected, morphine (1–8 mg/kg, IP) elicited a significant preference for the drug-paired compartment. Pretreatment of mice with (+)-dizocilpine (0.1 and 0.2 mg/kg, IP), the more active dizocilpine enantiomer, dose-dependently reversed the conditioned place preference produced by morphine (4 mg/kg, IP), whereas (–)-dizocilpine (0.2 mg/kg, IP) did not modify morphine-induced effects. In contrast, both enantiomers of dizocilpine (at a dose of 0.2 mg/kg, IP) elicited a conditioned place preference. These data suggest that (1) NMDA receptors play a role in morphine-induced place preference, and (2) dizocilpine-reinforcing properties in the place preference paradigm do not seem to be dependent on NMDA receptor blockade.