Design of a phencyclidine implantation pellet; Suitable for tolerance development.

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Abstract
When using laboratory animals (e.g., mice) for phencyclidine (PCP) [a drug of abuse] tolerance studies, an essential part of the procedure is to administer the PCP in such a way that the animals receive adequate doses of the drug at frequent enough intervals to reach and maintain the desired levels of tolerance; employment of an osmotic minipump which is either suitable or convenient to develop a high degree of tolerance to PCP in a large number of animals in a short period has also been suggested. These methods are unfit for routine work because repeated daily injections consume too much time and osmotic minipump is expensive. A PCP pellet suitable for tolerance development was developed. The s.c. implantation of a 10 or 20 mg PCP pellet in the back of a conscious mouse resulted in a much more rapid development of tolerance to PCP than that produced in mice receiving daily i.p. injection of 10 or 20 mg/kg PCP-HCl. Assessment of and the degree of tolerance to PCP by PCP pellet implantation and daily injection of PCP-HCl were evidenced by a decrease in the duration of motor incoordination after the challenge with 20 mg/kg, PCP-HCl 24 h after removal of PCP pellets or a last injection of PCP-HCl. Apparently, a substantial methodological improvement in producing a high degree of tolerance to PCP in a short period of time by means of the s.c. pellet implantation technique is shown.