Delayed application of MK-801 attenuates development of morphine tolerance in rats.
To investigate the possible involvement of enduring or delayed changes at the N-methyl-D-aspartic acid (NMDA) receptor in the mechanisms of morphine tolerance, rats were treated with the specific NMDA receptor antagonist, MK-801 (0.15 mg/kg) 2 h after morphine injection (20 mg/kg) during a 4-day induction period of tolerance. On the fifth day rats were injected only with morphine (15 mg/kg), and analgesia was assessed using the hot-plate test. Morphine tolerance was significantly reduced by MK-801. These findings suggest that long-lasting or delayed changes at the NMDA receptor underlie the development of morphine tolerance. Moreover, because MK-801 was delivered 2 h after morphine and therefore could not serve as a cue for morphine administration, these findings indicate that the attenuating effect of MK-801 on the development of morphine tolerance is not attributable to state-dependent learning.
Department of Psychology, University of California, Los Angeles 90024.
P
P
Marek
S
S
Ben-Eliyahu
A L
AL
Vaccarino
J C
JC
Liebeskind
D000704:Analysis of Variance; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004361:Drug Tolerance; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D016291:Dizocilpine Maleate; D009020:Morphine