腹侧纹状体低频-DBS可缩短吗啡场所偏好的持续时间并调节海马中BDNF的表达

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research Pub Date : 2024-10-28 DOI:10.1016/j.bbr.2024.115300

Mario E. Lloret-Torres, Jennifer L. Barreto-Estrada

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引用次数: 0

摘要

背景腹侧囊/腹侧纹状体（VC/VS）深部脑刺激（DBS）是一种治疗难治性药物滥用障碍患者的有前途的疗法。在本研究中，我们对动物进行了完全绝迹方案测试，以确定在绝迹过程中应用低频脑干刺激（LF-DBS）是否能在防止药物复吸的同时促进动物的绝迹，并研究低频脑干刺激（LF-DBS）作用的分子机制。然后在大脑皮质膜边缘区进行促消退分子脑源性神经营养因子（BDNF）的 Western 印迹检测。最后，为了确定LF-DBS引起的BDNF表达变化是否特异于海马、杏仁核和内侧前额叶皮层的VS/NAC传入，我们结合逆行示踪剂霍乱毒素B（CtB）进行了BDNF样免疫组化。结果我们发现，在消退训练期间暴露于 LF-DBS 的动物完全熄灭吗啡 CPP 所需的天数明显减少，同时海马中的 BDNF 表达明显增加。然而，在绝迹训练期间使用 LF-DBS 并不能阻止药物复吸。最后，在暴露于 LF-DBS 一天后，在 VS/NAc 投射细胞中没有发现 BDNF/CtB 双标记细胞的变化。

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LF-DBS of the ventral striatum shortens persistence for morphine place preference and modulates BDNF expression in the hippocampus

Background

Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) represents a promising therapy for treatment-refractory patients with substance-use disorders. We previously found that low-frequency (LF) DBS aimed to the VC/VS during extinction training strengthens the extinction memory for morphine seeking under a partial extinction protocol.

Objectives/Hypothesis

In this study, animals were tested in a full extinction protocol to determine whether LF-DBS applied during extinction facilitates extinction while preventing drug reinstatement, and study the molecular mechanisms underlying the effects of LF-DBS,

Methods/Results

We used a full extinction CPP paradigm combined with LF-DBS to assess behavior. Western blots for the pro-extinction molecule, brain-derived neurotrophic factor (BDNF) were then performed in corticomesolimbic regions of the brain. Lastly, to determine whether changes in BDNF expression elicited by LF-DBS were specific to the VS/NAc afferents from the hippocampus, amygdala, and medial prefrontal cortex, we performed BDNF-like immunohistochemistry, combined with the retrograde tracer cholera toxin B (CtB).

Results

We showed a significant reduction in the number of days required to fully extinguish morphine CPP in animals exposed to LF-DBS during extinction training accompanied by a significant increase in BDNF expression in the hippocampus. However, LF-DBS applied during extinction did not prevent drug reinstatement. Lastly, no changes in BDNF/CtB double-labeled cells were found in VS/NAc projecting cells after one-day exposure to LF-DBS.

Conclusion(s)

These data suggest that LF-DBS can facilitate extinction of morphine CPP by decreasing drug seeking through potential synaptic plasticity changes in the hippocampus to strengthen extinction memories.

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来源期刊

Behavioural Brain Research 医学-行为科学

CiteScore

5.60

自引率

0.00%

发文量

383

审稿时长

61 days

期刊介绍： Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.