Hammerbeck D M, Mitchell C L
J Pharmacol Exp Ther. 1978 Mar;204(3):558-69.
Twelve rhesus monkeys were studied under a fixed-ratio (FR) schedule of intravenous procaine or d-amphetamine injection from 8 A.M. to 4 P.M. daily. Under the FR schedule, every nth lever press produced an injection. The FR value (n) and the dose per injection of procaine and d-amphetamine were varied systematically. At a FR value of 10, responding was maintained by doses of procaine ranging from 0.125 to 12 mg/kg/injection and by doses of d-amphetamine ranging from 0.01 to 0.1 mg/kg/injection. At doses of 1 mg/kg/injection of procaine and 0.1 mg/kg/injection of d-amphetamine, responding was maintained at FR values up to 100 by procaine and d-amphetamine but not by saline. Responding and drug intake were relatively constant throughout each 8-hour session with procaine, but responding tended to decrease and was more variable over the session with d-amphetamine. No toxic effects were observed in doses up to 6 mg/kg/injection with procaine. At this dose, eating and drinking ceased during the period of access to the drug. One of the four monkeys died at 8 mg/kg/injection of procaine. At 12 mg/kg/injection all three monkeys tested showed signs of toxicity.
对12只恒河猴进行了研究,每天上午8点至下午4点按照固定比率(FR)时间表静脉注射普鲁卡因或右旋苯丙胺。在FR时间表下,每按压n次杠杆就会进行一次注射。系统地改变FR值(n)以及每次注射普鲁卡因和右旋苯丙胺的剂量。在FR值为10时,每注射一次,维持反应的普鲁卡因剂量范围为0.125至12毫克/千克,右旋苯丙胺剂量范围为0.01至0.1毫克/千克。每注射一次,当普鲁卡因剂量为1毫克/千克、右旋苯丙胺剂量为0.1毫克/千克时,在FR值高达100时,普鲁卡因和右旋苯丙胺可维持反应,但生理盐水不能。在每次8小时的普鲁卡因给药过程中,反应和药物摄入量相对恒定,但在右旋苯丙胺给药过程中,反应往往会下降,且在整个过程中变化更大。每注射一次,剂量高达6毫克/千克的普鲁卡因未观察到毒性作用。在此剂量下,给药期间进食和饮水停止。4只猴子中有1只在每注射一次剂量为8毫克/千克的普鲁卡因时死亡。每注射一次剂量为12毫克/千克时,所有3只接受测试的猴子均出现中毒迹象。