TMS effects on circuit plasticity and drug seeking in mice - Diversity Supplement

TMS 对小鼠回路可塑性和药物寻找的影响 - Diversity Supplement

• 批准号: 10393977
• 负责人: KHALED MOUSSAWI
• 金额: $ 1.71万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2021-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10393977
• 关键词: Address; Affect; Area; Brain; Clinical; Development; Distal; Drug Addiction; Epidemic; FDA approved; Fentanyl; Frequencies; Learning; Magnetism; Mental Depression; Morbidity - disease rate; Mus; Neurons; Nicotine Use Disorder; Olfactory tubercle; Opiate Addiction; Opioid; Pharmaceutical Preparations; Physiologic pulse; Protocols documentation; Research; Rewards; Therapeutic; Therapeutic Effect; Transcranial magnetic stimulation; Ventral Striatum; addiction; drug of abuse; effective therapy; mortality; mouse model; neuropsychiatric disorder; olfactory bulb; overdose death; piriform cortex; tool

Project Summary/Abstract Drug addiction is a leading cause of morbidity and mortality in the US. Opioid addiction in particular has become an epidemic with unprecedented overdose fatalities, half of which are caused by fentanyl. Our repertoire to treat opioid addiction is very limited, and the progress in finding effective treatments has stalled. Transcranial Magnetic Stimulation (TMS) is emerging as a potential therapeutic tool; it is currently FDA approved for depression and nicotine use disorder. This proposal will investigate the parameters of TMS use in a mouse model of opioid addiction. Through magnetic pulses, TMS non-invasively activates cortical neurons in the targeted area, resulting in brain-wide changes. However, several questions remain unanswered including whether intermittent Theta-Burst Stimulation (iTBS) with TMS induces long-lasting changes in downstream circuits beyond the targeted area, and how TMS affects distal brain circuits antidromically activated by TMS. This proposal will address these questions using TMS of the olfactory bulb in a mouse model. The hypothesis is that iTBS TMS of the olfactory bulb induces plasticity changes, more pronounced than high frequency stimulation protocols, in downstream circuits involved in learning and reward such as the piriform cortex and olfactory tubercle (part of the ventral striatum), and that different TMS protocols also induce antidromic plasticity in distal circuits which could underly some of the therapeutic effects of TMS.

项目总结/摘要 药物成瘾是美国发病率和死亡率的主要原因。阿片类药物成瘾 特别是已经成为一种流行病，前所未有的过量死亡，其中一半是 芬太尼引起的我们治疗阿片类药物成瘾的方法非常有限， 寻找有效的治疗方法已经停滞不前。经颅磁刺激（TMS）正在成为 一种潜在的治疗工具;目前FDA批准用于抑郁症和尼古丁使用 disorder.该提案将调查TMS在阿片样物质小鼠模型中使用的参数 成瘾通过磁脉冲，TMS非侵入性地激活大脑皮层神经元， 目标区域，导致大脑范围的变化。然而，有几个问题仍然没有答案 包括使用TMS的间歇性Theta-Burst刺激（iTBS）是否会引起长期的 目标区域以外的下游回路的变化，以及TMS如何影响远端大脑 经颅磁刺激（TMS）逆行激活回路。本提案将使用TMS解决这些问题 嗅球的一部分。假设嗅球的iTBS TMS 诱导可塑性变化，比高频刺激方案更明显， 参与学习和奖励的下游回路，如梨状皮质和嗅觉， 结节（腹侧纹状体的一部分），并且不同的TMS方案也会诱导逆向运动。 远端回路的可塑性，这可能是TMS治疗效果的基础。