迷走神经刺激对小胶质细胞抑制海洛因诱导的条件位置偏好的影响。

IF 8.8 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity Pub Date : 2025-03-01 DOI:10.1016/j.bbi.2025.02.031

Jianhua Bai , Yingbiao Yue , Zunyue Zhang , Kunhua Wang , Yun Jin , Junfeng Wang , Lei Zou

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引用次数: 0

摘要

背景：海洛因成瘾仍然是一个重大的全球健康挑战，有效的治疗方法有限。迷走神经刺激（VNS）在治疗各种神经系统疾病方面显示出希望，但其在成瘾治疗方面的潜力尚未得到探索。目的：探讨迷走神经刺激对海洛因诱导的条件性位置偏好（CPP）的影响，并阐明其神经生物学机制。方法：采用小鼠双侧膈下迷走神经切开术和VNS模型。经颈（nVNS）或经皮耳（taVNS）刺激后评估海洛因诱导的CPP。采用免疫荧光法和ELISA法观察伏隔核（NAc）小胶质细胞的活化情况。以甲基茄头碱为拮抗剂，研究了α7烟碱乙酰胆碱受体（α7nAChRs）的作用。结果：nVNS和taVNS均能显著减弱海洛因诱导的CPP。VNS逆转海洛因诱导的NAc小胶质细胞活化，降低促炎标志物和细胞因子，同时增加抗炎标志物。这些作用是由α - 7nachrs介导的，因为拮抗剂可以消除VNS的作用。值得注意的是，膈下迷走神经切开术不影响VNS的疗效，表明其主要的中枢作用机制。结论：VNS抑制海洛因诱导的CPP，可能通过α - 7nachr调节NAc小胶质细胞。taVNS虽然不如nVNS有效，但为成瘾治疗提供了一种很有前途的非侵入性方法。这些发现为进一步临床研究VNS，特别是taVNS作为海洛因成瘾的辅助治疗提供了理论依据。摘要：迷走神经刺激（VNS）通过α7烟碱乙酰胆碱受体调节伏隔核小胶质细胞的激活，从而减弱海洛因诱导的小鼠条件位置偏好。侵入性和非侵入性VNS均显示出疗效，后者具有作为一种新型成瘾治疗方法的潜力。这些发现为进一步研究VNS在海洛因成瘾管理中的临床应用提供了依据。

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Effects of vagus nerve stimulation on microglia inhibit heroin-induced conditional place preference

Background

Heroin addiction remains a significant global health challenge with limited effective treatments. Vagus nerve stimulation (VNS) has shown promise in treating various neurological disorders, but its potential in addiction treatment is unexplored.

Objective

To investigate the effects of VNS on heroin-induced conditioned place preference (CPP) and elucidate the underlying neurobiological mechanisms.

Methods

We employed bilateral subphrenic vagotomy and VNS models in mice. Heroin-induced CPP was assessed following transcervical (nVNS) or transcutaneous auricular (taVNS) stimulation. Microglial activation in the nucleus accumbens (NAc) was evaluated using immunofluorescence and ELISA. The role of α7 nicotinic acetylcholine receptors (α7nAChRs) was investigated using the antagonist methyllycaconitine.

Results

Both nVNS and taVNS significantly attenuated heroin-induced CPP. VNS reversed heroin-induced microglial activation in the NAc, reducing pro-inflammatory markers and cytokines while increasing anti-inflammatory markers. These effects were mediated by α7nAChRs, as antagonist administration abolished VNS efficacy. Notably, subphrenic vagotomy did not affect VNS efficacy, suggesting a primarily central mechanism of action.

Conclusion

VNS inhibits heroin-induced CPP, likely through modulation of NAc microglia via α7nAChRs. taVNS, while less effective than nVNS, offers a promising non-invasive approach to addiction treatment. These findings provide a rationale for further clinical investigation of VNS, particularly taVNS, as an adjunct therapy for heroin addiction.

Brief abstract

Vagus nerve stimulation (VNS) attenuates heroin-induced conditioned place preference in mice by modulating microglial activation in the nucleus accumbens via α7 nicotinic acetylcholine receptors. Both invasive and non-invasive VNS show efficacy, with the latter offering potential as a novel addiction treatment approach. These findings warrant further investigation of VNS in clinical settings for heroin addiction management.

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来源期刊

Brain, Behavior, and Immunity 医学-免疫学

CiteScore

29.60

自引率

2.00%

发文量

290

审稿时长

28 days

期刊介绍： Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals. As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.