Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats
Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats
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DOI：
10.1016/j.pbb.2005.12.015
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发表时间：
2006-01-01
影响因子：
3.6
通讯作者：
Woods, JH
中科院分区：
文献类型：
--
作者：
Fantegrossi, WE;Harrington, AW;Woods, JH
很少有研究检查了5-甲氧基-N，N-二异丙基色胺（5-MeO-DIPT）在体内的作用。在这些研究中，在药物引起的小鼠头部抽搐试验中测试了5-MeO-DIPT，其中将其与结构相似的致幻剂N，N-二甲基色胺（N，N-DMT）进行比较，并用选择性5-羟色胺（5-HT）（2A）拮抗剂M100907激发，在大鼠的麦角酰二乙胺（LSD）辨别试验中，用M100907或5-HT 1A选择性拮抗剂WAY激发其主观效应。100635.最后，在大鼠脑中测定5-MeO-DIPT对三种不同5-HT受体的亲和力。5-MeO-DIPT（而非N，N-DMT）诱导小鼠的头部抽搐反应，并且该作用可通过预先给予M100907而有效拮抗。在大鼠训练与LSD作为一个歧视性的刺激，有一个中等程度（75%）的泛化5-MeO-DIPT和剂量依赖性抑制的反应率。M100907消除了这些内感受性效应，但WAY-100635未显著减弱。5-MeO-DIPT对5-HT 2A和5-HT 2C受体具有微摩尔亲和力，但对5-HT 1A受体具有更高的亲和力。因此，5-MeO-DIPT在两种具有5-HT 2激动剂活性的啮齿动物模型中有效，并且对与致幻剂作用相关的受体具有亲和力。M 100907拮抗该化合物的行为作用的有效性，加上WAY-100635缺乏显著的拮抗作用，强烈表明5-HT 2A受体是5-MeO-DIPT的重要作用部位，尽管其对5-HT 1A受体具有明显的体外选择性。(C)2006年爱思唯尔公司All rights reserved.
Few studies have examined the effects of 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) in vivo. In these studies, 5-MeO-DIPT was tested in a drug-elicited head twitch assay in mice where it was compared to the structurally similar hallucinogen N,N-dimethyltryptamine (N,N-DMT) and challenged with the selective serotonin (5-HT)(2A) antagonist M100907, and in a lysergic acid diethylamide (LSD) discrimination assay in rats where its subjective effects were challenged with M100907 or the 5-HT1A selective antagonist WAY-100635. Finally, the affinity of 5-MeO-DIPT for three distinct 5-HT receptors was determined in rat brain. 5-MeO-DIPT, but not N,N-DMT, induced the head twitch responses in the mouse, and this effect was potently antagonized by prior administration of M100907. In rats trained with LSD as a discriminative stimulus, there was an intermediate degree (75%) of generalization to 5-MeO-DIPT and a dose-dependent suppression of response rates. These interoceptive effects were abolished by M100907, but were not significantly attenuated by WAY-100635. Finally, 5-MeO-DIPT had micromolar affinity for 5-HT2A and 5-HT2C receptors, but much higher affinity for 5-HT1A receptors. 5-MeO-DIPT is thus effective in two rodent models of 5-HT2 agonist activity, and has affinity at receptors relevant to hallucinogen effects. The effectiveness with which M 100907 antagonizes the behavioral actions of this compound, coupled with the lack of significant antagonist effects of WAY-100635, strongly suggests that the 5-HT2A receptor is an important site of action for 5-MeO-DIPT, despite its apparent in vitro selectivity for the 5-HT1A receptor. (C) 2006 Elsevier Inc. All rights reserved.