Attenuation of pharmacological effects and increased metabolism of phencyclidine in morphine tolerant mice.
Mice were used for a study of the interaction between morphine and phencyclidine (PCP) in relation to lethality, motor incoordination, locomotor activity and rearing, together with the half-life of PCP, following continuous administration of morphine by pellet (75 mg base) implantation for 72 h and after removal of the pellets for 6 and 24 h. PCP induced motor incoordination and suppressed locomotor activity and rearing; these effects were enhanced in morphine 'pellet-implanted' mice and were attenuated in morphine 'pellet-removed' groups. The enhancing effect of morphine on the PCP responses was attributable more to the presence of residual morphine than to the alterations in its disposition. The morphine-induced increase in locomotor activity and analgesia was attenuated in PCP (40 mg/kg per day i.p. for 5 days) tolerant mice. The rate of decay of PCP in serum and brain or morphine pellet-implanted animals was not different; however, in the 24 h 'pellet-removed' group, the rate of decay of PCP was increased. The results indicate that there is a two-way cross-tolerance development between PCP and morphine. The phenomenon appears to involve both dispositional and functional adaptation mechanisms.
D000818:Animals; D004347:Drug Interactions; D004361:Drug Tolerance; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000378:metabolism / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D010622:Phencyclidine / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity
D009020:Morphine; D010622:Phencyclidine