Middaugh L D, Favara J P, Boggan W O, Stringer A J
Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences, Charleston 29425-0742.
Psychopharmacology (Berl). 1988;96(3):381-4. doi: 10.1007/BF00216066.
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.
利用双杠杆操作性程序，在C57BL/6cr小鼠中研究了苯环己哌啶（PCP）的辨别特性及其对氯胺酮和单羟基化PCP代谢物作用的泛化。如先前对鸽子和大鼠的报道，在3.0mg/kg的训练剂量下，PCP在该物种中是可辨别的。PCP的辨别性泛化到不影响反应率的药物测试剂量（低至1.75mg/kg），也泛化到氯胺酮（10mg/kg）。两种PCP单羟基化代谢物在小鼠中均有活性。PCP部分泛化到单羟基化代谢物1-(1-苯基环己基)-4-羟基哌啶（PCHP），但不泛化到1-(1-苯基-4-羟基环己基)哌啶（PPC），这与先前关于大鼠的报道一致。PCP刺激对PCHP的泛化在小鼠中不如先前对大鼠的报道广泛，表明其在该物种中的效力可能较低。尽管PCP辨别性泛化到PCHP，但这种泛化需要PCHP的剂量，该剂量会产生比可辨别剂量的PCP所能导致的组织浓度高得多的浓度。因此，PCHP代谢物似乎并未介导C57BL/6cr小鼠中的PCP辨别性。
