Winter J C
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, 102 Farber Hall, Buffalo, NY 14214-3000, USA.
Psychopharmacology (Berl). 2009 Apr;203(2):251-63. doi: 10.1007/s00213-008-1356-8. Epub 2008 Nov 1.
Although man's first encounters with hallucinogens predate written history, it was not until the rise of the sister disciplines of organic chemistry and pharmacology in the nineteenth century that scientific studies became possible. Mescaline was the first to be isolated and its chemical structure determined. Since then, additional drugs have been recovered from their natural sources and synthetic chemists have contributed many more. Given their profound effects upon human behavior and the need for verbal communication to access many of these effects, some see humans as ideal subjects for study of hallucinogens. However, if we are to determine the mechanisms of action of these agents, establish hypotheses testable in human subjects, and explore the mechanistic links between hallucinogens and such apparently disparate topics as idiopathic psychosis, transcendental states, drug abuse, stress disorders, and cognitive dysfunction, studies in animals are essential. Stimulus control by hallucinogens has provided an intuitively attractive approach to the study of these agents in nonverbal species.
The intent of this review is to provide a brief account of events from the time of the first demonstration of hallucinogen-induced stimulus control to the present. In general, the review is limited to lysergic acid diethylamide (LSD) and the hallucinogenic derivatives of phenethylamine and tryptamine.
The pharmacological basis for stimulus control by LSD and hallucinogenic phenethylamines and tryptamines is serotonergic in nature. The 5-HT(2A) receptor appears to be the primary site of action with significant modulation by other serotonergic sites including 5-HT(2C) and 5-HT(1A) receptors. Interactions with other neurotransmitters, especially glutamate and dopamine, are under active investigation. Most studies to date have been conducted in the rat but transgenic mice offer interesting possibilities.
Hallucinogen-induced stimulus control provides a unique behavioral tool for the prediction of subjective effects in man and for the elucidation of the pharmacological mechanisms of the action of these agents.
尽管人类首次接触致幻剂的时间早于文字历史，但直到19世纪有机化学和药理学这两门姊妹学科兴起，科学研究才成为可能。麦司卡林是首个被分离出来并确定其化学结构的致幻剂。从那时起，其他药物也从天然来源中被提取出来，合成化学家又贡献了更多种类。鉴于这些药物对人类行为有深远影响，且需要通过言语交流来了解其中许多影响，一些人认为人类是研究致幻剂的理想对象。然而，如果我们要确定这些药物的作用机制，建立可在人体受试者中进行测试的假设，并探索致幻剂与诸如特发性精神病、超验状态、药物滥用、应激障碍和认知功能障碍等明显不同主题之间的机制联系，动物研究至关重要。致幻剂对行为的刺激控制为在非人类物种中研究这些药物提供了一种直观上有吸引力的方法。
本综述旨在简要介绍从首次证明致幻剂诱导的刺激控制到现在的相关事件。总体而言，本综述仅限于麦角酸二乙酰胺（LSD）以及苯乙胺和色胺的致幻衍生物。
LSD以及致幻性苯乙胺和色胺对行为的刺激控制的药理学基础本质上是5-羟色胺能的。5-HT(2A)受体似乎是主要作用位点，其他5-羟色胺能位点（包括5-HT(2C)和5-HT(1A)受体）有显著调节作用。与其他神经递质，尤其是谷氨酸和多巴胺的相互作用正在积极研究中。迄今为止，大多数研究是在大鼠中进行的，但转基因小鼠提供了有趣的可能性。
致幻剂诱导的刺激控制为预测人类主观效应以及阐明这些药物作用的药理学机制提供了一种独特的行为工具。
