Schindler C W, Goldberg S R, Katz J L
Preclinical Pharmacology Laboratory, National Institute on Drug Abuse, Baltimore, MD 21224.
Psychopharmacology (Berl). 1993;110(1-2):60-8. doi: 10.1007/BF02246951.
Rats treated weekly with cumulative doses (1-100 mg/kg, IP) of naltrexone develop an enhanced sensitivity to the operant response-rate decreasing effect of naltrexone. In the present experiment the pharmacological specificity of that enhanced sensitivity was determined by testing a variety of drugs for cross-sensitivity to naltrexone. Cross-sensitivity was evaluated with two procedures. In one, dose-effect functions were determined for each of the test compounds before and after the development of enhanced sensitivity to naltrexone in a single group of rats. In the second procedure, one group of rats was made sensitive to naltrexone, while a second was not. Test compounds were then evaluated in both groups. For both procedures, a shift to the left in the dose-effect functions similar to naltrexone was considered evidence of cross-sensitivity. Of the opioid antagonists tested, only naloxone showed clear cross-sensitivity to naltrexone, although MR 2266 and diprenorphine also showed evidence of cross-sensitivity. The opioid antagonist quadazocine did not show cross-sensitivity to naltrexone on the day of testing, although some evidence of cross-sensitivity was evident 24 h later. In addition, the dose-effect function for d-amphetamine was significantly changed following naltrexone treatment. No evidence of cross-sensitivity was observed for the optical isomer of naloxone, d-naloxone, or for naloxone's quaternary derivative, naloxone methiodide. None of the opioid agonists or agonist-antagonists tested showed cross-sensitivity to naltrexone (i.e. morphine, U-50, 488H, ethylketocyclazocine, N-allylnormetazocine and pentazocine). The non-opioid drugs chlordiazepoxide and phencyclidine also failed to show evidence of cross-sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)
每周腹腔注射累积剂量（1 - 100毫克/千克）纳曲酮的大鼠，对纳曲酮降低操作性反应率的作用产生增强的敏感性。在本实验中，通过测试多种药物对纳曲酮的交叉敏感性来确定这种增强敏感性的药理学特异性。交叉敏感性用两种方法评估。一种方法是，在一组大鼠对纳曲酮产生增强敏感性之前和之后，分别测定每种测试化合物的剂量 - 效应函数。第二种方法是，一组大鼠对纳曲酮敏感，而另一组不敏感。然后在两组中评估测试化合物。对于这两种方法，剂量 - 效应函数向左移动，类似于纳曲酮，被视为交叉敏感性的证据。在所测试的阿片类拮抗剂中，只有纳洛酮对纳曲酮表现出明显的交叉敏感性，尽管MR 2266和二丙诺啡也显示出交叉敏感性的证据。阿片类拮抗剂夸达佐辛在测试当天对纳曲酮未显示交叉敏感性，尽管24小时后有一些交叉敏感性的证据。此外，纳曲酮治疗后，右旋苯丙胺的剂量 - 效应函数发生了显著变化。未观察到纳洛酮的光学异构体d - 纳洛酮或纳洛酮的季铵衍生物甲基碘化纳洛酮有交叉敏感性的证据。所测试的阿片类激动剂或激动剂 - 拮抗剂均未对纳曲酮表现出交叉敏感性（即吗啡、U - 50,488H、乙基酮环唑辛、N - 烯丙基去甲左啡诺和喷他佐辛）。非阿片类药物氯氮卓和苯环己哌啶也未显示交叉敏感性的证据。（摘要截短于250字）
