Locke K W, Gorney B, Cornfeldt M, Fielding S
Department of Biological Research, Hoechst-Roussel Pharmaceuticals, Inc., Somerville, NJ 08876-1258.
Psychopharmacology (Berl). 1989;99(4):492-6. doi: 10.1007/BF00589897.
The opioid receptor selectivity of the EKC discriminative stimulus was characterized in Fischer rats trained to discriminate 0.3 mg/kg EKC (SC) from saline in a two-choice discrete-trial avoidance paradigm. The putative kappa-opioid receptor agonists EKC and U50,488H completely generalized with the EKC cue at doses of 0.3 and 10 mg/kg, respectively. The putative mu-opioid receptor agonists morphine (M) and fentanyl also dose-dependently generalized with the EKC stimulus. The generalization of M with EKC was not symmetrical, EKC and U50,488H produced little or no M-appropriate responding in rats trained to discriminate 3.0 mg/kg M (SC) from saline. This generalization pattern may reflect a lack of opioid receptor selectivity of the EKC stimulus. However, distinct mu-opioid and kappa-opioid components of the EKC cue could be identified using graded doses of naloxone in EKC-trained rats. The discriminative effects of morphine and fentanyl were blocked completely by doses of 0.1-1.0 mg/kg naloxone, whereas doses of naloxone 3-10 times greater were necessary to block the discriminative effects of EKC and U50,488H. These results suggest that EKC produces a complex discriminative stimulus with mu-opioid and kappa-opioid components that can be separated using antagonists such as naloxone.
在双选离散试验回避范式中，对费希尔大鼠进行训练，使其能够区分0.3毫克/千克艾考糊精（皮下注射）和生理盐水，以此来表征艾考糊精辨别刺激的阿片受体选择性。公认的κ-阿片受体激动剂艾考糊精和U50,488H分别在0.3毫克/千克和10毫克/千克的剂量下，能完全与艾考糊精线索产生泛化。公认的μ-阿片受体激动剂吗啡（M）和芬太尼也呈剂量依赖性地与艾考糊精刺激产生泛化。M与艾考糊精的泛化并不对称，在训练区分3.0毫克/千克M（皮下注射）和生理盐水的大鼠中，艾考糊精和U50,488H几乎没有或根本没有产生与M相应的反应。这种泛化模式可能反映出艾考糊精刺激缺乏阿片受体选择性。然而，在接受艾考糊精训练的大鼠中，使用不同剂量的纳洛酮可以识别出艾考糊精线索中不同的μ-阿片和κ-阿片成分。吗啡和芬太尼的辨别效应被0.1 - 1.0毫克/千克剂量的纳洛酮完全阻断，而阻断艾考糊精和U50,488H的辨别效应则需要3 - 10倍以上剂量的纳洛酮。这些结果表明，艾考糊精产生了一种具有μ-阿片和κ-阿片成分的复杂辨别刺激，使用纳洛酮等拮抗剂可以将其分离。
