神經科學家發現了LSD、mescaline及psilocybin等迷幻藥造成迷幻效果的機制，這項發現不僅解開了迷幻藥如何產生幻覺之謎，也有助于了解并找出治療神經精神病的路徑。 這項研究結果發表于2007年2月1 日的Neuron中。研究人員很久以前就知道迷幻藥會活化腦部的特殊受體5-HT2A，在正常的情況下，這種受體是由血清素所活化的。研究人員一直感到好奇的是，為什么有的物質會活化5-HT2A但卻不會引起幻覺。 在這項的研究中，研究人員利用小鼠的神經系統，比較LSD和也會活化5-HT2A之非迷幻物質的作用差異�？茖W家集中于研究小鼠腦部外皮，因為之前的研究顯示這是迷幻藥的作用中心。 研究分析顯示，LSD會導致一種遺傳性、電生理性、及細胞內部的信號反應，這種反應與非迷幻藥化合物造成的反應不同。研究人員發現，如果小鼠的5-HT2A受體不具功能，對于LSD就不會產生迷幻反應，但是如果恢復受體的功能，就會導致小鼠對于LSD的迷幻反應。
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 |
