The missing link: Opioid modulation of AMPA receptors

缺失的环节：阿片类药物对 AMPA 受体的调节

• 批准号: 2253144
• 金额: --
• 依托单位: University of Dundee
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2253144
• 关键词: missing; link; Opioid; modulation; AMPA

Major Depressive Disorder is a leading cause of global disability; however, current standard treatments are ineffective. The Lambert lab discovered that in the mouse hippocampus the pro-cognitive atypical antidepressant tianeptine employs a novel receptor crosstalk, activating delta-opioid receptors (DORs), increasing excitatory glutamatergic neurotransmission via calcium-permeable AMPA receptors (CP-AMPARs). However, the underlying biochemical signalling pathway is yet to be elucidated. Preliminary evidence implicates an involvement of CAMKII and PKA with a putative upstream involvement of the MAPK signalling pathway.This project will investigate the interactions between opioid and CP-AMPA receptors at the molecular, cellular and systems level using biochemical and electrophysiological techniques to gain a deeper understanding into this receptor crosstalk. Furthermore, this crosstalk has been implicated in synaptic plasticity, Events that lead to the release of endogenous opioids, such as mild stress or physical exercise, can enhance long-term potentiation (LTP) of synaptic strength. Therefore, the potential relationship between opioid receptors, CP-AMPARs and synaptic plasticity will be investigated.

重度抑郁症是全球残疾的主要原因;然而，目前的标准治疗无效。Lambert实验室发现，在小鼠海马中，促认知非典型抗抑郁药噻奈普汀采用了一种新的受体串扰，激活δ阿片受体（DORs），通过钙渗透性AMPA受体（CP-AMPAR）增加兴奋性阿片能神经传递。然而，潜在的生化信号通路尚未阐明。本项目将利用生物化学和电生理学技术，从分子、细胞和系统水平研究阿片受体和CP-AMPA受体之间的相互作用，以更深入地了解这种受体串扰。此外，这种串扰与突触可塑性有关。导致内源性阿片样物质释放的事件，如轻度应激或体育锻炼，可以增强突触强度的长时程增强（LTP）。因此，阿片受体，CP-AMPAR和突触可塑性之间的潜在关系将进行研究。