Development of dispositional tolerance to phencyclidine by osmotic minipump in the mouse.
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)-cytochrome 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.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004361:Drug Tolerance; D006207:Half-Life; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000201:enzymology; D010622:Phencyclidine / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity
D003577:Cytochrome P-450 Enzyme System; D010622:Phencyclidine