Iv. Belozertseva et al., Effects of short-acting NMDA receptor antagonist MRZ 2/576 on morphine tolerance development in mice, N-S ARCH PH, 361(6), 2000, pp. 573-577
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.