Negus S S, Morgan D, Cook C D, Picker M J
Alcohol and Drug Abuse Research Center, McLean Hospital-Harvard Medical School, Belmont, MA 01278, USA.
Psychopharmacology (Berl). 1996 Aug;126(3):199-205. doi: 10.1007/BF02246449.
The delta opioid agonist BW373U86 was examined alone and in combination with mu agonists in pigeons trained to discriminate the mu agonist fentanyl (0.056 mg/kg), the kappa agonist bremazocine (0.017 mg/kg), and distilled water in a three-choice drug discrimination procedure. BW373U86 (0.01-10 mg/kg) produced a dose-dependent increase in fentanyl-appropriate responding and complete generalization to fentanyl in four of five subjects. BW373U86 did not elicit bremazocine-appropriate responding in any of the subjects. Fentanyl-appropriate responding elicited by BW373U86 was antagonized by the delta selective antagonist naltrindole (0.1-10 mg/kg) but not by the mu selective antagonist naloxone (0.1-30.0 mg/kg). When BW373U86 was administered in combination with the mu agonists fentanyl, morphine and nalbuphine, a low dose of BW373U86 (0.01 mg/kg) that elicited primarily water-appropriate responding when administered alone did not produce a significant change in the ED50 values for fentanyl, morphine or nalbuphine. Higher doses of BW373U86 (0.1-1.0 mg/kg) increased levels of fentanyl-appropriate responding elicited by low doses of fentanyl, morphine and nalbuphine to levels similar to those produced by BW373U86 alone. These results indicate that BW373U86 shares discriminative stimulus properties with the mu agonist fentanyl in pigeons, possibly by acting at delta opioid receptors. However, BW373U86 does not potentiate the discriminative stimulus effects of mu agonists or share discriminative stimulus effects with the kappa agonist bremazocine.
在一个三选药物辨别程序中,对经训练能辨别μ阿片受体激动剂芬太尼(0.056毫克/千克)、κ阿片受体激动剂布马佐辛(0.017毫克/千克)和蒸馏水的鸽子,单独检测了δ阿片受体激动剂BW373U86,并检测了其与μ阿片受体激动剂联合使用的情况。BW373U86(0.01 - 10毫克/千克)使五分之四的实验对象出现了对芬太尼反应增加的剂量依赖性,并完全泛化为对芬太尼的反应。BW373U86在任何实验对象中均未引发对布马佐辛的适当反应。BW373U86引发的对芬太尼的适当反应被δ阿片受体选择性拮抗剂纳曲吲哚(0.1 - 10毫克/千克)拮抗,但未被μ阿片受体选择性拮抗剂纳洛酮(0.1 - 30.0毫克/千克)拮抗。当BW373U86与μ阿片受体激动剂芬太尼、吗啡和纳布啡联合给药时,单独给药时主要引发对水的适当反应的低剂量BW373U86(0.01毫克/千克),并未使芬太尼、吗啡或纳布啡的半数有效剂量(ED50)值产生显著变化。更高剂量的BW373U86(0.1 - 1.0毫克/千克)将低剂量芬太尼、吗啡和纳布啡引发的对芬太尼的适当反应水平提高到了与单独使用BW373U86时相似的水平。这些结果表明,BW373U86在鸽子中与μ阿片受体激动剂芬太尼具有共同的辨别性刺激特性,可能是通过作用于δ阿片受体。然而,BW373U86并不会增强μ阿片受体激动剂的辨别性刺激效应,也不会与κ阿片受体激动剂布马佐辛具有共同的辨别性刺激效应。