PDF(Pubmed)
Abstract：
Ibogaine (IBO) is an atypical psychedelic with a complex mechanism of action. To date, the mechanisms that may underlie its anti-addictive effects are still not defined. This study aims to identify changes in gene expression induced by a single oral dose of IBO in the cortex of mice by means of a transcriptomic analysis for the first time. Our results showed significant alterations in gene expression in mouse frontal cortex samples 4 h after a single oral dose of IBO. Specifically, genes involved in hormonal pathways and synaptogenesis exhibited upregulation, while genes associated with apoptotic processes and endosomal transports showed downregulation. The findings were further corroborated through quantitative polymerase chain reaction (qPCR) analysis. However, the validation of gene expression related to hormonal pathways did not entirely align with the transcriptomic analysis results, possibly due to the brain region from which tissue was collected. Sex differences were observed, with female mice displaying more pronounced alterations in gene expression after IBO treatment. High variability was observed across individual animals. However, this study represents a significant advancement in comprehending IBO\'s molecular actions. The findings highlight the influence of IBO on gene expression, particularly on hormonal pathways, synaptogenesis, apoptotic processes, and endosomal transports. The identification of sex differences underscores the importance of considering sex as a potential factor influencing IBO\'s effects. Further research to assess different time points after IBO exposure is warranted.
摘要：
伊波加因（IBO）是一种非典型的迷幻药，具有复杂的作用机制。迄今为止,可能构成其抗成瘾作用的机制仍未定义。这项研究旨在首次通过转录组学分析来确定单次口服IBO剂量在小鼠皮质中诱导的基因表达变化。我们的结果表明，单次口服IBO后4小时，小鼠额叶皮质样品中的基因表达发生了显着变化。具体来说,涉及激素途径和突触发生的基因表现出上调，而与凋亡过程和内体转运相关的基因显示下调。通过定量聚合酶链反应(qPCR)分析进一步证实了这些发现。然而,与激素途径相关的基因表达的验证与转录组学分析结果并不完全一致，可能是由于收集组织的大脑区域。观察到性别差异，雌性小鼠在IBO治疗后表现出更明显的基因表达变化。在个体动物中观察到高变异性。然而,这项研究在理解IBO的分子作用方面取得了重大进展。这些发现强调了IBO对基因表达的影响，特别是在荷尔蒙通路上，突触发生,凋亡过程，和内体转运。性别差异的识别强调了将性别视为影响IBO效应的潜在因素的重要性。需要进一步研究以评估IBO暴露后的不同时间点。
