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一种用于研究致幻剂的灵长类动物模型。

A primate model for the study of hallucinogens.

作者信息

Schlemmer R F, Davis J M

出版信息

Pharmacol Biochem Behav. 1986 Feb;24(2):381-92. doi: 10.1016/0091-3057(86)90368-0.

Abstract

An animal model for studying the actions of hallucinogenic drugs using primate social colonies is presented. Although hallucinogens induce a number of behavioral changes in this paradigm, one emergent behavior, limb jerks, appears to be selectively induced by three classes of hallucinogens in doses which correlate with those reported to be hallucinogenic in humans. Several non-hallucinogenic congeners of hallucinogens failed to significantly elicit this response. Other behavioral changes induced by hallucinogens in monkeys such as ptosis and social withdrawal may be useful in studying aspects of hallucinogen intoxication other than hallucinations, or psychosis in general. Upon daily administration, tolerance developed to all hallucinogens tested except two, as is seen in humans. Moreover, cross-tolerance between hallucinogens could be demonstrated. Further experiments with the hallucinogen 5-methoxy N,N-dimethyltryptamine revealed that although certain individual behaviors could be antagonized by serotonin antagonists, dopamine antagonists, and physostigmine, no drug completely reversed the behavioral abnormalities induced by this hallucinogen. It is suggested that this paradigm, which offers an hallucinogen-induced behavior which correlates well with the human hallucinogen response and permits observation of a wide variety of other potentially relevant behaviors in primates, may be useful in developing and testing theories of hallucinogenic drug action. It may be especially valuable in view of the present difficulties of conducting hallucinogen research in humans.

摘要

本文介绍了一种利用灵长类动物群居群体来研究致幻药物作用的动物模型。尽管在该模型中致幻剂会引发多种行为变化,但有一种新出现的行为,即肢体抽搐,似乎是由三类致幻剂在与据报道对人类有致幻作用的剂量相关的剂量下选择性诱导产生的。几种致幻剂的非致幻同系物未能显著引发这种反应。致幻剂在猴子身上引发的其他行为变化,如眼睑下垂和社交退缩,可能有助于研究除幻觉之外的致幻剂中毒方面,或一般的精神病情况。与人类一样,每天给药后,除了两种致幻剂外,对所有测试的致幻剂都产生了耐受性。此外,还可以证明致幻剂之间存在交叉耐受性。对致幻剂5-甲氧基-N,N-二甲基色胺的进一步实验表明,尽管某些个体行为可以被血清素拮抗剂、多巴胺拮抗剂和毒扁豆碱拮抗,但没有一种药物能完全逆转这种致幻剂所引发的行为异常。有人认为,这种模型提供了一种与人类致幻剂反应密切相关的致幻剂诱导行为,并允许观察灵长类动物中各种其他潜在相关行为,可能有助于发展和测试致幻药物作用的理论。鉴于目前在人类中进行致幻剂研究存在困难,它可能特别有价值。

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