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.

迷幻药物继续被大量人使用和滥用 在美国，最近人们对迷幻药物的作用重新产生了兴趣，例如 麦角酸二乙酰胺（LSD）。目前尚不清楚 LSD 及相关迷幻药物如何 在分子和原子水平上发挥其作用。在这个 MERIT 扩展中，我们将阐明 LSD及相关药物与多个G蛋白偶联的相互作用的分子机制 受体。我们还将确定人类和啮齿动物之间差异的潜在相关性 LSD 和相关药物在体外和体内作用的受体。最后我们将检查 LSD 和相关药物对基因转录变化的影响，这些变化特别发生在 表达 LSD 作用所必需的受体的神经元。综合起来，这些新发现 将提供有关迷幻药物在体外和体内作用的分子和原子细节 体内。 相关性（参见说明）： 在这笔资助中，我们将阐明 LSD 在分子水平上发挥作用的分子细节。 我们将结合迷幻受体与 LSD 和相关药物复合的结构研究。我们 还将探讨啮齿动物和人类受体之间的特定差异的作用以及 迷幻药物作用下游的转录变化。