Neuron：研究人员发现迷幻药的作用机制
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神经科学家发现了LSD、mescaline及psilocybin等迷幻药造成迷幻效果的机制，这项发现不仅解开了迷幻药如何产生幻觉之谜，也有助于了解并找出治疗神经精神病的路径。
这项研究结果发表于2007年2月1 日的Neuron中。研究人员很久以前就知道迷幻药会活化脑部的特殊受体5-HT2A，在正常的情况下，这种受体是由血清素所活化的。研究人员一直感到好奇的是，为什么有的物质会活化5-HT2A但却不会引起幻觉。
在这项的研究中，研究人员利用小鼠的神经系统，比较LSD和也会活化5-HT2A之非迷幻物质的作用差异。科学家集中于研究小鼠脑部外皮，因为之前的研究显示这是迷幻药的作用中心。
研究分析显示，LSD会导致一种遗传性、电生理性、及细胞内部的信号反应，这种反应与非迷幻药化合物造成的反应不同。研究人员发现，如果小鼠的5-HT2A受体不具功能，对于LSD就不会产生迷幻反应，但是如果恢复受体的功能，就会导致小鼠对于LSD的迷幻反应。
部分英文原文：
Hallucinogens Recruit Specific Cortical 5-HT2A Receptor-Mediated Signaling Pathways to Affect Behavior
Javier González-Maeso1, 7, Noelia V. Weisstaub3, 4, 5, 7, Mingming Zhou4, Pokman Chan1, Lidija Ivic1, Rosalind Ang1, Alena Lira4, Maria Bradley-Moore4, Yongchao Ge1, 2, Qiang Zhou1, Stuart C. Sealfon1, 2, , and Jay A. Gingrich4, 5, 6
1Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA
2Center for Translational Systems Biology, Mount Sinai School of Medicine, New York, NY 10029, USA
3Department of Biological Sciences, Columbia University, New York, NY 10032, USA
4Department of Psychiatry, Columbia University, New York, NY 10032, USA
5Sackler Institute Laboratories, New York State Psychiatric Institute, New York, NY 10032, USA
6Lieber Center for Schizophrenia Research, New York State Psychiatric Institute, New York, NY 10032, USA
Received 6 July 2006; revised 27 November 2006; accepted 10 January 2007. Published: January 31, 2007. Available online 31 January 2007.
Summary
Hallucinogens, including mescaline, psilocybin, and lysergic acid diethylamide (LSD), profoundly affect perception, cognition, and mood. All known drugs of this class are 5-HT2A receptor (2AR) agonists, yet closely related 2AR agonists such as lisuride lack comparable psychoactive properties. Why only certain 2AR agonists are hallucinogens and which neural circuits mediate their effects are poorly understood. By genetically expressing 2AR only in cortex, we show that 2AR-regulated pathways on cortical neurons are sufficient to mediate the signaling pattern and behavioral response to hallucinogens. Hallucinogenic and nonhallucinogenic 2AR agonists both regulate signaling in the same 2AR-expressing cortical neurons. However, the signaling and behavioral responses to the hallucinogens are distinct. While lisuride and LSD both act at 2AR expressed by cortex neurons to regulate phospholipase C, LSD responses also involve pertussis toxin-sensitive heterotrimeric Gi/o proteins and Src. These studies identify the long-elusive neural and signaling mechanisms responsible for the unique effects of hallucinogens.
Author Keywords: MOLNEURO; SIGNALING; HUMDISEASE
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