Oliveto A H, Picker M J, Dykstra L A
Department of Psychology, University of North Carolina, Chapel Hill 27599-3270.
J Pharmacol Exp Ther. 1991 Apr;257(1):8-18.
The effects of several opioid compounds were examined in rats and squirrel monkeys responding under a fixed-ratio 30 schedule of food presentation. In rats, dose-effect curves were determined before and after acute pretreatment with 5.6 mg/kg of morphine 5 to 6 hr before the session, as well as during and after the termination of a chronic regimen in which rats received 30.0 mg/kg/day of morphine. In monkeys, dose-effect curves were determined before, during and after the termination of a chronic regimen in which monkeys received 6.0 mg/kg/day of morphine. In morphine-pretreated rats, dose-effect curves for the opioid antagonists naloxone, naltrexone and diprenorphine shifted to the left of those determined when rats were not morphine-pretreated; whereas those for the mu-opioid agonists morphine and I-methadone and mixed-action opioids nalorphine, nalbuphine, butorphanol, pentazocine and bremazocine were unaltered. During chronic morphine administration in rats, dose-effect curves for morphine and butorphanol shifted to the right; whereas the dose-effect curves for naloxone and nalorphine shifted to the left of those determined when rats were not treated with morphine. The effects of pentazocine, nalbuphine, bremazocine and the kappa-opioid agonist U50,488 were unaltered in morphine-maintained rats. In morphine-maintained monkeys, the dose-effect curves for morphine and I-methadone shifted to the right; whereas those for naloxone, nalorphine and nalbuphine shifted to the left of the prechronic dose-effect curves. Dose-effect curves for butorphanol, pentazocine and U50,488 were unaltered. Overall, these results suggest that the chronic morphine administration procedure can be used to distinguish opioid compounds based upon their relative mu agonist and antagonist activity.
在按固定比率30的食物呈现时间表做出反应的大鼠和松鼠猴中，研究了几种阿片类化合物的作用。在大鼠中，在实验前5至6小时用5.6毫克/千克吗啡进行急性预处理之前和之后，以及在大鼠接受30.0毫克/千克/天吗啡的慢性给药方案期间和结束后，测定剂量 - 效应曲线。在猴子中，在猴子接受6.0毫克/千克/天吗啡的慢性给药方案之前、期间和结束后，测定剂量 - 效应曲线。在经吗啡预处理的大鼠中，阿片类拮抗剂纳洛酮、纳曲酮和二丙诺啡的剂量 - 效应曲线向未用吗啡预处理的大鼠所测定曲线的左侧移动；而μ阿片类激动剂吗啡和左美沙酮以及混合作用阿片类药物纳洛芬、纳布啡、布托啡诺、喷他佐辛和布瑞吗唑的曲线未改变。在大鼠慢性吗啡给药期间，吗啡和布托啡诺的剂量 - 效应曲线向右移动；而纳洛酮和纳洛芬的剂量 - 效应曲线向未用吗啡治疗的大鼠所测定曲线的左侧移动。喷他佐辛、纳布啡、布瑞吗唑和κ阿片类激动剂U50,488在吗啡维持的大鼠中的作用未改变。在吗啡维持的猴子中，吗啡和左美沙酮的剂量 - 效应曲线向右移动；而纳洛酮、纳洛芬和纳布啡的曲线向慢性给药前剂量 - 效应曲线的左侧移动。布托啡诺、喷他佐辛和U50,488的剂量 - 效应曲线未改变。总体而言，这些结果表明，慢性吗啡给药程序可用于根据阿片类化合物相对的μ激动剂和拮抗剂活性来区分它们。
