Effects of short-acting NMDA receptor antagonist MRZ 2/576 on morphine tolerance development in mice

The present study sought to evaluate the ability of a short-acting glycine( B) site NMDA receptor antagonist. MRZ 2/576, to affect morphine tolerance d evelopment in mice. It was found that MRZ 2/576 (10 mg/kg, i.p.) significan tly retarded development of morphine analgesic tolerance (20 mg/kg, s.c., 8 days, once a day; tail-flick test) when administered 120 min or 150 min af ter each daily morphine injection. MRZ 2/576 did not affect the development of morphine tolerance when administered immediately, 15, 30, 60, 90, 180, 240, 300 or 360 min after the daily morphine injections. Thus, short-acting NMDA receptor antagonists may be useful in exploring the temporal characte ristics of opioid tolerance (i.e., peri ods after morphine injection that a re critical for tolerance induction) and the present study suggests that af ter morphine administration there is a period of NMDA receptors activation crucial for the development of tolerance.