Li Jun-Xu, Rice Kenner C, France Charles P
Department of Pharmacology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
J Pharmacol Exp Ther. 2008 Feb;324(2):827-33. doi: 10.1124/jpet.107.130625. Epub 2007 Nov 9.
Discriminative stimulus effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) and related drugs have been studied extensively in rodents, although the generality of those findings across species is not known. The goals of this study were to see whether monkeys could discriminate DOM and to characterize the DOM discriminative stimulus by studying a variety of drugs, including those with hallucinogenic activity in humans. Four rhesus monkeys discriminated between 0.32 mg/kg s.c. DOM and vehicle after an average of 116 (range = 85-166) sessions while responding under a fixed ratio 5 schedule of stimulus shock termination. Increasing doses of DOM occasioned increased responding on the drug lever with the training dose occasioning DOM-lever responding for up to 2 h. The serotonin (5-HT)(2A/2C) receptor antagonists ritanserin and ketanserin, the 5-HT(2A) receptor antagonist (+)2,3-dimethoxyphenyl-1-[2-(4-piperidine)-methanol] (MDL100907), and its (-)stereoisomer MDL100009 [(-)2,3-dimethoxyphenyl-1-[2-(4-piperidine)-methanol], but not haloperidol, completely blocked the discriminative stimulus effects of DOM. Quipazine as well as several drugs with hallucinogenic activity in humans, including (+)lysergic acid diethylamide, (-)DOM, and 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7), occasioned DOM-lever responding. The kappa-opioid receptor agonists U-50488 and salvinorin A (a hallucinogen) did not exert DOM-like effects and neither did ketamine, phencyclidine, amphetamine, methamphetamine, cocaine, morphine, yohimbine, fenfluramine, 8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT), or (+/-)-2-(N-phenethyl-N-1'-propyl)amino-5-hydroxytetralin hydrochloride (N-0434). These data confirm in nonhuman primates a prominent role for 5-HT(2A) receptors in the discriminative stimulus effects of some drugs with hallucinogenic activity in humans. The failure of another drug with hallucinogenic activity (salvinorin A) to substitute for DOM indicates that different classes of hallucinogens exert qualitatively different discriminative stimulus effects in nonhumans.
1-（2,5-二甲氧基-4-甲基苯基）-2-氨基丙烷（DOM）及相关药物的辨别刺激效应已在啮齿动物中得到广泛研究，不过这些研究结果在不同物种间的普遍性尚不清楚。本研究的目的是观察猴子是否能辨别DOM，并通过研究多种药物，包括在人类中具有致幻活性的药物，来表征DOM的辨别刺激。四只恒河猴在平均116次（范围=85 - 166次）实验后，能在0.32毫克/千克皮下注射DOM和溶剂之间做出辨别，同时在固定比率5的刺激休克终止程序下做出反应。DOM剂量增加会导致药物杠杆上的反应增加，训练剂量能使DOM杠杆反应持续长达2小时。5-羟色胺（5-HT）（2A/2C）受体拮抗剂利坦色林和酮色林、5-HT（2A）受体拮抗剂（+）2,3-二甲氧基苯基-1-[2-（4-哌啶）-甲醇]（MDL100907）及其（-）立体异构体MDL100009 [（-）2,3-二甲氧基苯基-1-[2-（4-哌啶）-甲醇]，但不是氟哌啶醇，完全阻断了DOM的辨别刺激效应。喹哌嗪以及几种在人类中具有致幻活性的药物，包括（+）麦角酸二乙胺、（-）DOM和2,5-二甲氧基-4-（n）-丙基硫代苯乙胺（2C-T-7），引发了DOM杠杆反应。κ-阿片受体激动剂U-50488和Salvinorin A（一种致幻剂）未产生类似DOM的效应，氯胺酮、苯环己哌啶、苯丙胺、甲基苯丙胺、可卡因、吗啡、育亨宾、芬氟拉明、8-羟基-2-（二丙基氨基）四氢溴化萘（8-OH-DPAT）或（+/-）-2-（N-苯乙基-N-1'-丙基）氨基-5-羟基四氢萘盐酸盐（N-0434）也未产生类似效应。这些数据在非人灵长类动物中证实了5-HT（2A）受体在某些在人类中具有致幻活性的药物的辨别刺激效应中起重要作用。另一种具有致幻活性的药物（Salvinorin A）不能替代DOM，这表明不同类别的致幻剂在非人类中产生的辨别刺激效应在性质上有所不同。
