Wenger G R
J Pharmacol Exp Ther. 1983 Jun;225(3):646-52.
In order to determine whether tolerance developed to the behavioral effects of phencyclidine, pigeons were trained to respond under a multiple fixed-ratio 30, fixed-interval 600-sec schedule of food presentation. When rates and patterns of responding reached stability, dose-response curves for phencyclidine (0.1-10 mumol/kg i.m.), ketamine (3-56 mumol/kg i.m.) and pentobarbital (1-75 mumol/kg i.m.) were determined. Phencyclidine, ketamine and pentobarbital all decreased fixed-ratio 30 responding in a dose-related manner and increased fixed-internal 600-sec. responding at immediate doses. At higher doses, pentobarbital decreased responding. High doses of phencyclidine and ketamine suppressed responding in the early portions of the session, but when responding returned, it returned at a high rate. After 35 daily injections of phencyclidine (3 mumol/kg/day i.m.), dose-response curves were redetermined for all three drugs. A tolerance was observed for moderate doses of phencyclidine, and a moderate cross-tolerance was observed to ketamine. No tolerance was observed for the total suppression of responding produced by high doses of phencyclidine and ketamine early in the test sessions. No cross-tolerance to pentobarbital was observed. After 215 days of daily phencyclidine administration, no withdrawal signs were observed upon the discontinuation of daily injections.
为了确定对苯环己哌啶行为效应是否产生耐受性，训练鸽子在多重固定比率30、固定间隔600秒的食物呈现时间表下做出反应。当反应速率和模式达到稳定后，测定苯环己哌啶（0.1 - 10 μmol/kg，肌肉注射）、氯胺酮（3 - 56 μmol/kg，肌肉注射）和戊巴比妥（1 - 75 μmol/kg，肌肉注射）的剂量 - 反应曲线。苯环己哌啶、氯胺酮和戊巴比妥均以剂量相关的方式降低固定比率30反应，并在即刻给药时增加固定间隔600秒的反应。在较高剂量时，戊巴比妥降低反应。高剂量的苯环己哌啶和氯胺酮在实验期早期抑制反应，但当反应恢复时，恢复速率很高。在每天肌肉注射苯环己哌啶（3 μmol/kg/天）35天后，重新测定了所有三种药物的剂量 - 反应曲线。观察到对中等剂量的苯环己哌啶产生耐受性，对氯胺酮观察到中等程度的交叉耐受性。在实验期早期，高剂量的苯环己哌啶和氯胺酮对反应的完全抑制未观察到耐受性。未观察到对戊巴比妥的交叉耐受性。在每天给予苯环己哌啶215天后，停止每日注射时未观察到戒断症状。
