McMillan D E, Leander J D
J Pharmacol Exp Ther. 1978 Nov;207(2):515-20.
Dose-effect curves were determined in rats for the effects of drugs on punished and unpunished responding maintained by fixed-interval schedules of food presentation before, during and after the drinking of large daily doses of chlordiazepoxide and pentobarbital. An average intake of 50 mg/kg/day of chlordiazepoxide produced tolerance to the rate-decreasing effects of chlordiazepoxide on unpunished responding and cross-tolerance to the rate-decreasing effects of pentobarbital. During chlordiazepoxide drinking, rate-increasing effects of both chlordiazepoxide and pentobarbital on punished responding became apparent. There was no evidence for cross-tolerance between chlordiazepoxide and chlorpromazine. An average intake of 100 mg/kg/day of pentobarbital produced similar evidence of tolerance to the rate-decreasing effects of pentobarbital on unpunished responding and cross-tolerance to the rate-decreasing effects of chlordiazepoxide. Removal of chlordiazepoxide from the drinking water temporarily increased unpunished responding; however, 6 weeks after withdrawal of chlordiazepoxide or pentobarbital from the drinking water, the dose-effect curves for injections of these drugs appeared to be returning to their original positions.
在大鼠中测定了药物对按固定间隔食物呈现时间表维持的受罚和不受罚反应的剂量-效应曲线，实验分别在大鼠每日大量饮用氯氮卓和戊巴比妥之前、期间和之后进行。平均每日摄入50mg/kg的氯氮卓会产生对氯氮卓对不受罚反应的速率降低效应的耐受性，以及对戊巴比妥的速率降低效应的交叉耐受性。在饮用氯氮卓期间，氯氮卓和戊巴比妥对受罚反应的速率增加效应变得明显。没有证据表明氯氮卓和氯丙嗪之间存在交叉耐受性。平均每日摄入100mg/kg的戊巴比妥会产生类似的耐受性证据，即对戊巴比妥对不受罚反应的速率降低效应的耐受性，以及对氯氮卓的速率降低效应的交叉耐受性。从饮用水中去除氯氮卓会暂时增加不受罚反应；然而，在从饮用水中停用氯氮卓或戊巴比妥6周后，注射这些药物的剂量-效应曲线似乎正在恢复到原来的位置。
