Hutchinson A C, Simpson G R, Randall J F, Zhang X, Calderon S N, Rice K C, Riley A L
Psychopharmacology Laboratory, Department of Psychology, American University, Washington, DC 20016, USA.
Pharmacol Biochem Behav. 2000 Aug;66(4):779-87. doi: 10.1016/s0091-3057(00)00278-1.
Although compounds with relative selectivity for the mu and kappa opiate receptors subtypes have been reported to condition taste aversions, it is not known whether systemically administered delta compounds have the ability to produce aversions. To that end, female Long-Evans rats were adapted to water deprivation and were given pairings of a novel saccharin solution and various doses of the selective delta agonist SNC 80 (0.32-10.0 mg/kg; Experiment 1) or the selective delta antagonist naltrindole (1.0-18.0 mg/kg; Experiment 2). For comparison, the relatively selective mu agonist morphine (Experiment 1) and mu antagonist naloxone (Experiment 2) were assessed under identical conditions. Both SNC 80 (Experiment 1) and naltrindole (Experiment 2) were effective as unconditioned stimuli within this design, inducing dose-dependent taste aversions with repeated conditioning trials. Although at no dose did animals injected with SNC 80 differ from those injected with morphine, aversions induced by SNC 80 were acquired at a faster rate than those induced by morphine. Subjects injected with naloxone drank significantly less than those injected with naltrindole at the 10 mg/kg dose, and aversions induced by naloxone at 5.6 and 10 mg/kg were acquired at a faster rate than those induced by naltrindole. Although the basis for opioid agonist- and antagonist-induced taste aversions is not known, the differences between aversions induced by SNC 80 and naltrindole and those induced by morphine and naloxone, respectively, may be a function of their relative selectivity for specific opiate receptor subtypes.
尽管据报道,对μ和κ阿片受体亚型具有相对选择性的化合物可引发味觉厌恶,但尚不清楚全身给药的δ化合物是否具有产生厌恶的能力。为此,对雌性Long-Evans大鼠进行缺水适应处理,并将一种新型糖精溶液与各种剂量的选择性δ激动剂SNC 80(0.32 - 10.0 mg/kg;实验1)或选择性δ拮抗剂纳曲吲哚(1.0 - 18.0 mg/kg;实验2)进行配对。为作比较,在相同条件下评估了相对选择性的μ激动剂吗啡(实验1)和μ拮抗剂纳洛酮(实验2)。在该实验设计中,SNC 80(实验1)和纳曲吲哚(实验2)均作为非条件刺激有效,通过重复条件试验诱导出剂量依赖性味觉厌恶。尽管注射SNC 80的动物在任何剂量下与注射吗啡的动物均无差异,但SNC 80诱导的厌恶比吗啡诱导的厌恶获得速度更快。在10 mg/kg剂量下,注射纳洛酮的受试者饮水量显著少于注射纳曲吲哚的受试者,并且5.6和10 mg/kg剂量的纳洛酮诱导的厌恶比纳曲吲哚诱导的厌恶获得速度更快。尽管阿片类激动剂和拮抗剂诱导味觉厌恶的机制尚不清楚,但SNC 80和纳曲吲哚分别与吗啡和纳洛酮诱导的厌恶之间的差异,可能是它们对特定阿片受体亚型相对选择性的作用结果。