Developing a reverse translational model of low-intensity rTMS in alcohol use disorder: The influence of theta burst stimulation protocols on binge alcohol drinking in mice.

Transcranial magnetic stimulation (2024) Pub Date : 2025-08-01 Epub Date: 2025-04-18 DOI:10.1016/j.transm.2025.100098

Akriti Dhungana, Daniel M McCalley, Alesha M Heath, Eric P Kraybill, Fatemeh S Mojabi, Jairelisse Morales Morales, Allison R Morningstar, Allyson K Davis, Claudia B Padula, William J Giardino, M Windy McNerney

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Abstract

Background: Repetitive Transcranial Magnetic Stimulation (rTMS) is a promising treatment tool for Alcohol Use Disorder (AUD). A challenge facing the field is that the optimal TMS parameters to reduce drinking are unknown. There are now rodent TMS coils which can be adapted to evaluate rTMS-induced changes in alcohol consumption in a rapid, cost-effective manner.

Objective: Develop a preclinical model of rTMS in alcohol consuming rodents and collect pilot data to evaluate the influence rTMS parameters (here, theta burst pattern) on change in alcohol consumption and biochemistry.

Methods: 66 C57BL/6 J mice (32 F) received sham, intermittent Theta Burst Stimulation (iTBS), or continuous Theta Burst Stimulation (cTBS) (14 sessions, 2 sessions/day, low intensity 16mT stimulation). Alcohol consumption and preference were evaluated before and after rTMS using a two-bottle choice, Drinking in the Dark (DID) paradigm. Cortical brain tissue was assayed for BDNF gene expression via qPCR. During DID sessions, control mice (n = 31) were given access to water only.

Results: Relative to sham, iTBS increased alcohol consumption (d=0.72) and preference (d=0.44), however these results were not statistically significant. Female mice receiving iTBS, experienced a significant, large increase in alcohol consumption (p = 0.02, d=1.5). Among water only mice, iTBS (d=-1.01) and cTBS (d=-1.03) significantly reduced BDNF expression.

Conclusions: This preclinical model is a feasible method to evaluate rTMS-induced changes in alcohol consumption. This pilot analysis warrants future work evaluating the influence of rTMS parameters and sex on changes in drinking or drug-seeking behaviors.

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在酒精使用障碍中建立低强度rTMS的反向翻译模型：θ波爆发刺激方案对小鼠暴饮的影响。

背景：重复经颅磁刺激（rTMS）是一种很有前途的治疗酒精使用障碍（AUD）的工具。该领域面临的一个挑战是，减少饮酒的最佳经颅磁刺激参数是未知的。现在有啮齿类动物经颅磁刺激线圈，可用于以快速、经济有效的方式评估经颅磁刺激引起的酒精消费变化。目的：建立酒精消耗啮齿动物rTMS临床前模型，收集中试数据，评估rTMS参数（这里为θ波爆发模式）对酒精消耗和生物化学变化的影响。方法：66只C57BL/6 J小鼠（32 F）分别接受假刺激、间歇θ波爆发刺激（iTBS）和连续θ波爆发刺激（cTBS）（14次，2次/天，低强度16mT刺激）。在rTMS之前和之后，使用两瓶选择，在黑暗中饮酒（DID）范式评估酒精消费和偏好。采用qPCR检测脑组织皮层BDNF基因表达。在DID期间，对照组小鼠（n = 31）只给予水。结果：与假手术相比，iTBS增加了酒精摄入（d=0.72）和偏好（d=0.44），但这些结果没有统计学意义。接受iTBS的雌性小鼠的酒精消耗量显著增加（p = 0.02, d=1.5）。在纯水小鼠中，iTBS （d=-1.01）和cTBS （d=-1.03）显著降低BDNF表达。结论：该临床前模型是评估rtms诱导的酒精消耗变化的可行方法。这一初步分析为未来评估rTMS参数和性别对饮酒或寻求药物行为变化的影响提供了依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Transcranial magnetic stimulation (2024)

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