Discriminative properties of phencyclidine in mice: generalization to ketamine and monohydroxy metabolites

The discriminative properties of phencyclidine (PCP) and their generalization to the effects of ketamine and monohydroxylated PCP metabolites were examined in C57BL/6cr mice utilizing two-lever operant procedures. As previously reported for pigeons and rats, PCP was discriminable in this species at a training dose of 3.0 mg/kg. PCP discriminability generalized to test doses of the drug that did not influence response rates (as low as 1.75 mg/kg) and also to ketamine (10 mg/kg). Both PCP monohydroxylated metabolites were active in mice. PCP partially generalized to the monohydroxylated metabolite, 1-(1-phenylcyclohexyl)4-hydroxy piperidine (PCHP) but not to 1-(1-phenyl-4-hydroxycyclohexyl) piperidine (PPC), which is consistent with previous reports on rats. The generalization of the PCP stimulus to PCHP was not as extensive in mice as previously reported for rats, suggesting that it may be less potent in this species. Although PCP discriminability generalized to PCHP, this generalization required PCHP doses that would produce tissue concentrations much higher than could result from discriminable doses of PCP. Therefore, the PCHP metabolite does not appear to mediate PCP discriminability in C57BL/6cr mice.