Attenuation of pharmacological effects and increased metabolism of phencyclidine in morphine tolerant mice

Toshitaka Nabeshima, Subbiah P. Sivam, Ing K. Ho

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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.

Original languageEnglish
Pages (from-to)211-221
Number of pages11
JournalEuropean Journal of Pharmacology
Issue number3-4
Publication statusPublished - 17-09-1984
Externally publishedYes


All Science Journal Classification (ASJC) codes

  • Pharmacology

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