Carroll M E
Drug Alcohol Depend. 1982 Jul;9(3):213-24. doi: 10.1016/0376-8716(82)90046-1.
Three rhesus monkeys self-administered fixed doses (4, 8 or 16 mg/kg) of an orally-delivered phencyclidine solution (0.25 mg/ml) under a one response, fixed-ratio (FR 1) schedule. They self-administered a saccharin 0.05% (wt/vol) solution, under an FR 8 schedule, 40 minutes after phencyclidine access began. After behavior stabilized over at least five daily sessions at each dose, water was substituted for phencyclidine for four sessions, and then phencyclidine was reinstated at the same dose, and behavior was allowed to stabilize. A comparison of saccharin-maintained behavior before and after the four sessions of water substitution yielded a two-fold shift in the dose effect curve indicating a rapid loss of tolerance to phencyclidine. Phencyclidine produced a biphasic effect on saccharin-maintained behavior: response rates increased at the low dose and decreased at the high dose. Subsequently, the FR requirement for saccharin was increased to 16 and the number of sessions of water substitution was varied: 1, 4, 8 or 16. The results indicated that tolerance was lost after four days of phencyclidine absence but not one, and complete tolerance was acquired within four to five days. This procedure produced a reliable measure of tolerance under limited access conditions whereby orally-delivered phencyclidine was also demonstrated to be functioning as a reinforcer.
三只恒河猴在单一反应、固定比率（FR 1）的实验安排下，自行服用口服苯环己哌啶溶液（0.25毫克/毫升）的固定剂量（4、8或16毫克/千克）。在开始服用苯环己哌啶40分钟后，它们在FR 8的实验安排下自行服用0.05%（重量/体积）的糖精溶液。在每种剂量下，行为在至少五个每日实验阶段稳定后，用水替代苯环己哌啶进行四个实验阶段，然后以相同剂量恢复使用苯环己哌啶，并让行为稳定下来。对四个水替代实验阶段前后糖精维持行为的比较显示，剂量效应曲线有两倍的偏移，表明对苯环己哌啶的耐受性迅速丧失。苯环己哌啶对糖精维持行为产生双相效应：低剂量时反应率增加，高剂量时反应率降低。随后，将糖精的FR要求提高到16，并改变水替代的实验阶段数：1、4、8或16。结果表明，在没有苯环己哌啶的四天后耐受性丧失，一天后则没有，并且在四到五天内获得了完全耐受性。该程序在有限接触条件下产生了一种可靠的耐受性测量方法，据此口服苯环己哌啶也被证明起到了强化剂的作用。
