Investigating long-term, post-acute effects of psychedelics on cognitive function: neurobiological and psychological mechanisms

牛津大学罗盘路径实验心理学该项目旨在为更好地理解啮齿动物体内5-羟色胺能药物--特别是5-羟色胺迷幻剂--与灵活的行为和认知之间的关系奠定基础。认知灵活性被认为在发展轨迹、人生成功和健康老龄化方面发挥着重要作用(Uddin Nat Rev Neurosci 2021)，而灵活性缺陷是几种神经和精神疾病的核心组成部分。此外，5-羟色胺能信号与灵活的认知密切相关，5-羟色胺靶向药物是治疗一系列此类大脑疾病的既定疗法。因此，这项研究可能会在几个不同的学科(例如心理学、神经生理学、精神病学、神经学)中产生广泛的影响。然而，重要的是，关于不同的5-羟色胺能药物如何发挥治疗效果，仍然没有达成多少共识。这既适用于传统的抗抑郁药物，如5-羟色胺再摄取抑制剂(SSRIs)，也适用于新型5-羟色胺能迷幻药物。采用系统神经科学的方法来理解5-羟色胺能迷幻药如何影响灵活行为，并将其与SSRIs的影响进行对比，可能会引起包括Compass Path在内的公司对研究新的有效疗法的预测因素的高度兴趣。此外，学生将受益于该项目中的想法、活体技术和分析方法，这些方法只有在英国的几个研究所才有。这将使他们能够在未来将这些技能传播到其他学术或行业职位。我们致力于根据BBSRC的政策，免费提供我们研究产生的所有数据，使各个领域的学者能够最大限度地受益。特别是，电生理数据集将引起计算建模领域的强烈兴趣，允许测试现有模型并为随后的测试开发新的假设。BBSRC主题-对健康的综合理解的生物科学

Experimental Psychology, University of Oxford COMPASS Pathways This project aims to lay the foundations for a better understanding of the mechanisms underlying the relationship between serotonergic pharmacology - particularly serotonin psychedelics - and flexible behaviour and cognition in the rodent. Cognitive flexibility is thought to play an important role in developmental trajectories, life success and healthy ageing (Uddin Nat Rev Neurosci 2021), and deficits in flexibility form a core component of several neurological and psychiatric diseases. Moreover, serotonergic signalling is strongly implicated in flexible cognition, and serotonin-targeting drugs are established therapies for a range of these brain disorders. Therefore, the research will likely have a wide sphere of influence across several different disciplines (e.g., psychology, neurophysiology, psychiatry, neurology). Importantly, however, there is still little consensus as to how different serotonergic drugs exert their therapeutic effects. This is the case both for conventional anti-depressant medications such as serotonin reuptake inhibitors (SSRIs) and also for novel serotonergic psychedelic drugs. Taking a systems neuroscience approach to understanding how serotonergic psychedelics influence flexible behaviour, and contrasting this with the influence of SSRIs, is potentially of high interest to companies - including COMPASS Pathways - investing in researching predictors of new effective therapies. In addition, the student will benefit by exposure to ideas, in vivo techniques and analytical approaches in the project that are only available in a few UK institutes. This will allow them to propagate these skills to other academic or industrial positions in the future. We are committed to make all data arising from our studies freely available, in line with the BBSRC policy, enabling maximum benefit to academics across a range of fields. In particular, the electrophysiological data set will be of strong interest to the computational modelling field, allowing testing of existing models and the development of new hypotheses for subsequent testing.BBSRC theme - Bioscience for an integrated understanding of health