Mechanistic insights into LSD actions at 5-HT2A serotonin receptors

LSD 对 5-HT2A 血清素受体作用的机制见解

• 批准号: 10550420
• 负责人: Bryan L. Roth
• 金额: $ 66.45万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10550420
• 关键词: Complex; Drug Interactions; G-Protein-Coupled Receptors; Genetic Transcription; Grant; HTR2A gene; Hallucinogens; Human; In Vitro; Individual; Instruction; Lysergic Acid Diethylamide; Molecular; Neurons; Pharmaceutical Preparations; Rodent; Role; drug action; in vivo; insight; interest; receptor; serotonin receptor

Psychedelic drugs continue to be used and abused by large numbers of individuals within the US and recently there has been a resurgence of interest in the actions of psychedelic drugs like lysergic acid diethylamide (LSD). It is currently unknown how LSD and related psychedelic drugs exert their actions at the molecular and atomic levels. In this MERIT extension we will elucidate the molecular mechanisms by which LSD and related drugs interact with multiple G protein coupled receptors. We will also determine the potential relevance of differences between human and rodent receptors for the actions of LSD and related drugs in vitro and in vivo. Finally we will examine the effects of LSD and related drugs on the gene transcriptional changes which occur specifically in neurons which express receptor essential for the actions of LSD. Taken together, these new findings will provide molecular and atomic details regading the actions of psychedelic drugs in vitro and in vivo. RELEVANCE (See instructions): In this grant we will illuminate the molecular details responsible for LSD's actions at the molecular level. We will combine structural studies of psychedelic receptors complexed with LSD and related drugs. We will also interrogate the role of specific differences between rodent and human receptors as well as transcriptional changes downstream of psychedelic drug actions.

迷幻药物继续被世界各地大量个人使用和滥用 最近，人们对迷幻药物的作用重新产生了兴趣，比如 麦角酸二乙胺(LSD)。目前尚不清楚LSD和相关迷幻药物是如何 在分子和原子层面发挥它们的作用。在这一优点扩展中，我们将阐明 LSD及相关药物与多个G蛋白偶联的分子机制 感受器。我们还将确定人类和啮齿动物之间的差异的潜在相关性。 LSD及相关药物的体外和体内作用受体。最后，我们将研究 LSD及相关药物对小鼠脑内特异性基因转录变化的影响 表达LSD作用所必需的受体的神经元。综合来看，这些新发现 将提供迷幻药物在体外和体内的作用的分子和原子细节 活着。 相关性(请参阅说明)： 在这项资助中，我们将阐明在分子水平上导致LSD作用的分子细节。 我们将结合与LSD和相关药物复合的迷幻受体的结构研究。我们 也将询问啮齿动物和人类受体之间的特定差异以及 迷幻药物作用下游的转录变化。