Competitive roles of slow/delta oscillation-nesting-mediated sleep disruption under acute methamphetamine exposure in monkeys

Xin LV; Jie LIU; Shuo MA; Yuhan WANG; Yixin PAN; Xian QIU; Yu CAO; Bomin SUN; Shikun ZHAN

doi:10.1631/jzus.B2400048

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Research Article | Updated：2025-07-25

Competitive roles of slow/delta oscillation-nesting-mediated sleep disruption under acute methamphetamine exposure in monkeys
Competitive roles of slow/delta oscillation-nesting-mediated sleep disruption under acute methamphetamine exposure in monkeys
甲基苯丙胺急性暴露通过影响慢波与delta振荡的竞争性耦合作用破坏恒河猴睡眠稳态
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 26, Issue 7, Pages: 694-707(2025)
Affiliations：

1.Center of Functional Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
2.Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
3.Department of Nursing, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai 200025, China
4.Shanghai Jiao Tong University School of Nursing, Shanghai 200025, China
5.Shandong Mental Health Center, Jinan 250014, China
Funds：
DOI：10.1631/jzus.B2400048
CLC：
CSTR：
Received：30 January 2024，

Revised：09 May 2024，

Published Online：23 June 2025，

Published：15 July 2025
Accepted：

吕鑫,刘杰,马硕等.甲基苯丙胺急性暴露通过影响慢波与delta振荡的竞争性耦合作用破坏恒河猴睡眠稳态[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(07):694-707.

Xin LV, Jie LIU, Shuo MA, et al. Competitive roles of slow/delta oscillation-nesting-mediated sleep disruption under acute methamphetamine exposure in monkeys[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(7): 694-707.
吕鑫,刘杰,马硕等.甲基苯丙胺急性暴露通过影响慢波与delta振荡的竞争性耦合作用破坏恒河猴睡眠稳态[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(07):694-707. DOI： 10.1631/jzus.B2400048.

Xin LV, Jie LIU, Shuo MA, et al. Competitive roles of slow/delta oscillation-nesting-mediated sleep disruption under acute methamphetamine exposure in monkeys[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(7): 694-707. DOI： 10.1631/jzus.B2400048.

摘要

苯丙胺类兴奋剂的滥用是全球重要的公共健康风险之一。近期研究指出，处方安非他命类药物的滥用呈现显著上升趋势。然而，急性甲基苯丙胺暴露（AME）影响睡眠稳态的神经生理机制仍有待探索。本研究采用非人灵长类动物（恒河猴）为模型，利用脑电图（EEG）睡眠分期的方法评估AME对神经振荡的调控作用，并重点研究AME对睡眠纺锤波、delta波和慢波（SO）的差异性影响，及其在睡眠稳定性调控中的相互作用机制。AME显著抑制非快速眼动2期（NREM2）的睡眠纺锤波，并对SO和delta波具有差异性调控作用。此外，甲基苯丙胺特异性增强了SO和delta波与睡眠纺锤波的嵌套关系；复杂度特征分析发现，SO嵌套的纺锤波维持睡眠深度和稳定性的生理功能也出现显著损伤。上述结果在神经振荡网络层面上阐述了AME导致睡眠稳态破坏的内在电生理机制。

Abstract

Abuse of amphetamine-based stimulants is a primary public health concern. Recent studies have underscored a troubling escalation in the inappropriate use of prescription amphetamine-based stimulants. However

the neurophysiological mechanisms underlying the impact of acute methamphetamine exposure (AME) on sleep homeostasis remain to be explored. This study employed non-human primates and electroencephalogram (EEG) sleep staging to evaluate the influence of AME on neural oscillations. The primary focus was on alterations in spindles

delta oscillations

and slow oscillations (SOs) and their interactions as conduits through which AME influences sleep stability. AME predominantly diminishes sleep-spindle waves in the non-rapid eye movement 2 (NREM2) stage

and impacts SOs and delta waves differentially. Furthermore

the competitive relationships between SO/delta waves nesting with sleep spindles were selectively strengthened by methamphetamine. Complexity analysis also revealed that the SO-nested spindles had lost their ability to maintain sleep depth and stability. In summary

this finding could be one of the intrinsic electrophysiological mechanisms by which AME disrupted sleep homeostasis.

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references

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