Development of dispositional tolerance to phencyclidine by osmotic minipump in the mouse

Nabeshima Toshitaka, Subbiah P. Sivam, Christine Y. Tai, Ing K. Ho

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23 Citations (Scopus)


Development of tolerance to phencyclidine (PCP) was assessed in male ICR mice, using motor incoordination as a parameter. The implantation of a PCP (1-3 mg/ day/mouse for 1-5 days)-containing osmotic minipump, induced tolerance, as evidenced by a gradual reduction of the duration of motor incoordination. The degree of tolerance exhibited dose and time dependency. Even after the removal of the PCP pump (1 mg/day/mouse for 5 days), the tolerance remained to the same degree for at least 4 days. The hepatic microsomal cytochrome P-450, cytochrome b5 and nicotinamide adenine dinucleotide phosphatase (NADPH)-cyctochrome c reductase activities were found to be elevated in tolerant mice (2 mg/ day/mouse for 5 days). The half-life of PCP in the brains of tolerant mice was likewise decreased. These data indicate a dispositional tolerance for PCP. It appears that the administration of PCP by the osmotic minipump offers a convenient method for inducing PCP tolerance.

Original languageEnglish
Pages (from-to)239-253
Number of pages15
JournalJournal of Pharmacological Methods
Issue number3
Publication statusPublished - 05-1982
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology


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