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Sex differences in stress-modulated cocaine vulnerability: female rodents are more sensitive to the effects of stress exposure at different developmental stages. 压力调节可卡因脆弱性的性别差异:雌性啮齿动物在不同发育阶段对压力暴露的影响更敏感。
IF 2.9 3区 医学 Q2 BEHAVIORAL SCIENCES Pub Date : 2025-12-09 eCollection Date: 2025-01-01 DOI: 10.3389/fnbeh.2025.1689548
María Ángeles Martínez-Caballero, Claudia Calpe-López, Maria Pilar García-Pardo, M Carmen Arenas, Carmen Manzanedo, María A Aguilar

Introduction: Stressful life events can trigger the initiation of cocaine use, facilitate the transition to a cocaine-use disorder (CUD), and precipitate relapse. Evidence suggests that women progress more rapidly to a CUD than men. Thus, the influence of stressful life events on CUD development may differ by sex, contributing to the enhanced vulnerability seen among females. In this work, we provide a comprehensive (non-systematic) review of clinical and preclinical studies comparing the effects of cocaine and its modulation by stress in both sexes.

Methods: We performed a search of the PubMed database (1986-2025) in which we combined the keywords "cocaine" and "stress" with "sex differences" or "female rat" or "female mice" or "women." We then read the abstracts of the search results to select potentially relevant studies, which we read in full to determine if they fulfilled our criteria and to extract the relevant information.

Results: Sex is often overlooked as a biological variable in preclinical and clinical research. The results of clinical studies indicate the existence of sex differences in the response to stress among individuals with CUD. Preclinical studies strongly suggest that female rodents are more vulnerable to developing addiction-like features than male rodents, particularly in the self-administration paradigm. Furthermore, exposure to stress appears to amplify the effects of cocaine, especially in females.

Discussion: There is growing evidence that women and female rodents are more vulnerable to the behavioral and neurochemical changes that characterize cocaine addiction. The influence of sex should be considered in research and in the selection of strategies for preventing and treating CUD, including those targeting stress reduction.

简介:生活中的压力事件可引发可卡因使用的开始,促进向可卡因使用障碍(CUD)的过渡,并促使复发。有证据表明,女性比男性更快地发展为反刍腹泻。因此,压力生活事件对CUD发展的影响可能因性别而异,导致女性的脆弱性增加。在这项工作中,我们对临床和临床前研究进行了全面(非系统)的回顾,比较了可卡因的影响及其在两性压力下的调节作用。方法:我们对PubMed数据库(1986-2025)进行了搜索,我们将关键词“可卡因”和“压力”与“性别差异”或“雌性大鼠”或“雌性小鼠”或“女性”结合起来。然后,我们阅读搜索结果的摘要,以选择可能相关的研究,我们全文阅读,以确定它们是否符合我们的标准,并提取相关信息。结果:在临床前和临床研究中,性别作为一个生物学变量经常被忽视。临床研究结果表明,CUD患者对压力的反应存在性别差异。临床前研究强烈表明,雌性啮齿动物比雄性啮齿动物更容易出现成瘾样特征,特别是在自我给药范式中。此外,暴露在压力下似乎会放大可卡因的作用,尤其是对女性而言。讨论:越来越多的证据表明,女性和雌性啮齿动物更容易受到可卡因成瘾特征的行为和神经化学变化的影响。在研究和选择预防和治疗CUD的策略,包括以减轻压力为目标的策略时,应考虑到性别的影响。
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引用次数: 0
Rethinking stress in education: cortisol and DHEA-S biomarker outcomes of a mindset intervention. 重新思考教育中的压力:一种心态干预的皮质醇和DHEA-S生物标志物结果。
IF 2.9 3区 医学 Q2 BEHAVIORAL SCIENCES Pub Date : 2025-12-09 eCollection Date: 2025-01-01 DOI: 10.3389/fnbeh.2025.1685319
Ari Langrafe Junior, Luiz Claudio Fernandes, Evandro Moraes Peixoto, Anita Nishiyama

Objective: Teacher stress is a global concern with significant consequences for health, performance, and educational quality. While most studies address stress as a harmful phenomenon, emerging evidence suggests that an individual's mindset toward stress can influence both psychological and physiological outcomes. This study investigated whether a brief video-based mindset intervention could alter stress perception and modulate biological stress markers among public school teachers in Brazil.

Methods: A randomized controlled trial was conducted with 63 teachers allocated into intervention (n = 32) and control (n = 31) groups. The intervention group received an 8-days series of short educational videos developed by Stanford University's Mind and Body Lab, designed to promote a growth-oriented stress mindset. Measures included the Stress Mindset Measure (SMM), Perceived Stress Scale (PSS-10), Stroop Color Task, and salivary biomarkers (cortisol and DHEA-S). Data were collected at baseline, post-intervention, and 30-days follow-up. Analyses included repeated measures ANOVA and t-tests.

Results: The intervention significantly improved stress mindset scores immediately after the intervention and at follow-up (p < 0.001; ε2 = 0.664), with no change in the control group. Cortisol concentrations decreased significantly in the intervention group post-intervention (p = 0.004; ε2 = 0.262), though the effect was not maintained after 30 days. No significant changes were observed in DHEA-S levels. Additionally, cognitive performance on the Stroop incongruent task improved significantly in the intervention group (p = 0.003; d = 0.565), suggesting enhanced executive functioning under stress.

Discussion: The findings support the effectiveness of a brief, low-cost intervention in shifting stress mindsets and producing acute physiological and cognitive benefits. However, the transient nature of the hormonal response underscores the need for sustained or complementary strategies to reinforce long-term stress resilience. This study highlights the value of mindset-based approaches in educational settings and their potential for improving teacher well-being through psychoneuroendocrinological mechanisms.

目的:教师压力是一个全球关注的问题,对健康、表现和教育质量产生重大影响。虽然大多数研究认为压力是一种有害的现象,但新出现的证据表明,个人对压力的心态会影响心理和生理结果。本研究调查了一个简短的基于视频的心态干预是否可以改变巴西公立学校教师的压力感知和调节生物压力标记。方法:采用随机对照试验方法,将63名教师分为干预组(n = 32)和对照组(n = 31)。干预组接受了由斯坦福大学身心实验室开发的一系列为期8天的教育短片,旨在促进以成长为导向的压力心态。测量包括压力心态测量(SMM)、感知压力量表(PSS-10)、Stroop颜色任务和唾液生物标志物(皮质醇和DHEA-S)。在基线、干预后和30天随访时收集数据。分析包括重复测量、方差分析和t检验。结果:干预后即刻及随访时压力心态得分均有显著提高(p < 0.001; ε2 = 0.664),对照组无显著变化。干预组皮质醇浓度在干预后显著降低(p = 0.004; ε2 = 0.262),但30天后效果未维持。DHEA-S水平未见明显变化。此外,干预组在Stroop不一致任务上的认知表现显著改善(p = 0.003; d = 0.565),表明压力下执行功能增强。讨论:研究结果支持一种简短、低成本的干预方法在改变压力心态和产生急性生理和认知益处方面的有效性。然而,激素反应的短暂性强调了需要持续或互补的策略来加强长期的应激恢复力。这项研究强调了基于心态的方法在教育环境中的价值,以及它们通过心理神经内分泌机制改善教师幸福感的潜力。
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引用次数: 0
The effects of spaced versus massed extinction training on extinction retention of conditioned fear learning in male rats. 间隔与大规模消退训练对雄性大鼠条件恐惧学习消退记忆的影响。
IF 2.9 3区 医学 Q2 BEHAVIORAL SCIENCES Pub Date : 2025-12-09 eCollection Date: 2025-01-01 DOI: 10.3389/fnbeh.2025.1727468
Grant W LeVasseur, Timothy Cilley, Michelle Szewczuk, Shane A Perrine, Seth D Norrholm

Introduction: Extinction learning of conditioned fear behavior has been used as a translational model to study human fear-, anxiety-, trauma-, and stressor-related disorders and their underlying neurobiology in animal models because the underlying neural processes of extinction learning are fundamental to the most effective clinical interventions for these disorders. Specifically, extinction-based prolonged exposure therapy is the first-line, gold-standard, cognitive behavioral treatment for fear-, trauma-, stressor-, and anxiety-based disorders. However, the ways that parametric differences in methodologies alter extinction learning are still not well understood.

Methods: Therefore, in the current study, we altered the number of days on which an equal number of extinction trials were presented in an extinction of conditioned fear learning-paradigm. As part of this paradigm, we employed fear-potentiated startle as a primary outcome measure of fear responses in adult, male rats. One group received 120 massed extinction trials in 1 day, a second group received 120 extinction trials across 2 days, and a final group received 120 extinction trials spaced across 4 days. We hypothesized that a greater number of days of extinction training would lead to improved extinction retention.

Results: We found minimal differences between groups on the final test of extinction retention, although increased fear behaviors were observed at the start of the second day of extinction training in the 2-day group.

Discussion: These findings have implications with respect to the flexibility of fear extinction methodologies employed as well as to how data generated from chosen paradigms is interpreted.

在动物模型中,条件性恐惧行为的消退学习被用作研究人类恐惧、焦虑、创伤和压力相关疾病及其潜在神经生物学的翻译模型,因为消退学习的潜在神经过程是对这些疾病最有效的临床干预的基础。具体来说,基于灭绝的长时间暴露疗法是第一线、黄金标准的认知行为治疗,用于治疗基于恐惧、创伤、压力源和焦虑的疾病。然而,方法论中的参数差异改变灭绝学习的方式仍然没有得到很好的理解。方法:因此,在本研究中,我们改变了在条件恐惧消退学习范式中呈现相同数量的消退试验的天数。作为这个范例的一部分,我们使用恐惧增强惊吓作为成年雄性大鼠恐惧反应的主要结果测量。第一组在1天内接受120次大规模灭绝试验,第二组在2天内接受120次灭绝试验,最后一组在4天内接受120次灭绝试验。我们假设,更多的灭绝训练天数将导致更好的灭绝保留。结果:我们发现两组之间在最终测试中的差异很小,尽管在2天组的第2天训练开始时观察到恐惧行为增加。讨论:这些发现涉及到所采用的恐惧消除方法的灵活性,以及如何解释从选择的范例中产生的数据。
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引用次数: 0
Automated thermal gradient test for unprovoked assessment of nociceptive preference in rodents. 自动热梯度测试对啮齿动物伤害性偏好的无端评估。
IF 2.9 3区 医学 Q2 BEHAVIORAL SCIENCES Pub Date : 2025-12-05 eCollection Date: 2025-01-01 DOI: 10.3389/fnbeh.2025.1709160
Thomas Deakin, Shoupeng Wei, Yao Wang, Raina E Rhoades, Tommy S Tillman, Pei Tang, Yan Xu

In animal models, reflexive responses to noxious stimuli (e.g., paw withdrawal in von Frey, Hargreaves, or cold plantar tests) are largely spinal reflexes and their quantitative measures (latency or threshold) may not directly reflect clinically relevant pain perception as assessed by human quantitative sensory testing, which captures both conscious sensory and affective components of pain as a subjective experience. This study aims to develop a complementary behavioral testing strategy for rapidly and automatically detecting rodents' thermal responses under different pain conditions without human interference. A device is engineered to create a linear thermal gradient from 4 °C to 58 °C along a long aluminum floor of four equal-size corridors, each having a dimension of 137 cm × 10 cm × 22 cm (L × W × H) and allowing four freely roaming rodents to be simultaneously evaluated to increase the throughput of in vivo pain testing. Animal behaviors influenced by the temperature gradient are recorded by a camera and analyzed using ANY-Maze. The duration of data collection is investigated, showing that the data collected in as short as 10 min can adequately capture thermal preferences of mice along the temperature gradient. Animal behaviors reveal differences in thermal nociception between male and female mice, capture counterintuitive changes in nociceptive thermal avoidance in the absence and presence of inflammatory pain, and show analgesic effects of morphine (10 mg/kg subcutaneously) as well as its stimulation of hyperactive locomotion. The sensitivity, reliability, and efficiency of the new thermal gradient test will not only help mechanistic investigations of various thermal sensing receptors but also enable high-throughput in vivo pain evaluation and analgesic drug screening for developing new treatments for pain management.

在动物模型中,对有害刺激的反射性反应(如von Frey、Hargreaves或冷足底试验中的爪子退缩)主要是脊柱反射,其定量测量(潜伏期或阈值)可能不能直接反映临床相关的疼痛感知,而人类定量感觉测试评估了疼痛的有意识感觉和情感成分作为主观体验。本研究旨在开发一种无需人工干预快速自动检测不同疼痛条件下啮齿动物热反应的互补行为测试策略。设计了一种装置,可以沿着四条大小相等的走廊的长铝地板产生从4°C到58°C的线性热梯度,每个走廊的尺寸为137厘米× 10厘米× 22厘米(长×宽×高),允许四只自由漫游的啮齿动物同时进行评估,以增加体内疼痛测试的吞吐量。用摄像机记录温度梯度对动物行为的影响,并用ANY-Maze分析动物行为。研究了数据收集的持续时间,结果表明,在10分钟内收集的数据可以充分捕捉小鼠沿温度梯度的热偏好。动物行为揭示了雄性和雌性小鼠在热伤害感受上的差异,捕捉到了在没有和存在炎症性疼痛时伤害性热回避的反直觉变化,并显示了吗啡(10 mg/kg皮下注射)的镇痛作用及其对过度活跃运动的刺激。新的热梯度测试的灵敏度、可靠性和效率不仅有助于各种热感受体的机制研究,而且可以实现高通量的体内疼痛评估和镇痛药物筛选,为开发新的疼痛治疗方法提供帮助。
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引用次数: 0
Bright light exposure reduces negative affect and modulates EEG activity in sleep-deprived and well-rested adolescents. 在睡眠不足和休息良好的青少年中,强光照射可减少负面影响并调节脑电图活动。
IF 2.9 3区 医学 Q2 BEHAVIORAL SCIENCES Pub Date : 2025-12-04 eCollection Date: 2025-01-01 DOI: 10.3389/fnbeh.2025.1673093
Jana Kopřivová, Zuzana Kaňková, Přemysl Vlček, Marek Piorecký, Lenka Maierová, Zdeňka Bendová, Kateřina Skálová, Tereza Nekovářová

Introduction: This study investigated whether a single morning session of bright light exposure modulates alertness, cognition, mood, and EEG activity in well-rested and partially sleep-deprived adolescents.

Methods: Forty-seven subjects (15-21 years) were assigned to a well-rested (8 h sleep; 9 men, 15 women) or a sleep-deprived group (4 h sleep; 11 men, 12 women). All underwent 30 min of morning bright light exposure, with EEG, cognitive testing, and ratings of sleepiness and affect conducted pre- and post-intervention. Behavioral and electrophysiological changes were compared within and between groups. Associations between changes in EEG activity and behavioral outcomes were explored using correlation analyses.

Results: Bright light significantly reduced negative affect and improved Digit Span Forward task performance. No changes were observed in positive affect, subjective sleepiness, or Digit Span Backward scores. EEG analysis revealed decreased delta activity in the anterior cingulate cortex and increased beta activity in the right insula and fronto-parietal regions. Behavioral and EEG effects were similar across groups; however, only in the sleep-deprived group changes in beta activity significantly correlated with reduced negative affect.

Discussion: These results suggest that bright light may acutely enhance emotional state, cognitive performance, and cortical arousal in adolescents. The link between beta activity and affective improvement under sleep deprivation suggests a potential mechanism by which light supports emotional regulation.

本研究调查了在休息良好和部分睡眠不足的青少年中,单次晨光照射是否会调节警觉性、认知、情绪和脑电图活动。方法:47名研究对象(15-21岁)被分为睡眠充足组(8小时睡眠,9名男性,15名女性)和睡眠不足组(4小时睡眠,11名男性,12名女性)。所有人都接受了30分钟的晨光照射,并在干预前后进行了脑电图、认知测试、困倦和影响评分。比较各组内和组间的行为和电生理变化。利用相关分析探讨脑电图活动变化与行为结果之间的关系。结果:明亮灯光显著降低负性情绪,提高数字跨距前向任务的表现。在积极影响、主观困倦或数字广度向后得分方面没有观察到变化。脑电图分析显示,前扣带皮层的δ活动减少,右侧脑岛和额顶叶区域的β活动增加。各组间行为和脑电图效果相似;然而,只有在睡眠不足的一组中,β活动的变化与消极情绪的减少显著相关。讨论:这些结果表明,明亮的光线可能会显著增强青少年的情绪状态、认知表现和皮层觉醒。在睡眠剥夺的情况下,β活动和情感改善之间的联系暗示了光支持情绪调节的潜在机制。
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引用次数: 0
Correction: Generalized tonic-clonic seizures as the initial symptom of late-onset Krabbe disease: a Case Report. 更正:全身性强直-阵挛性发作作为迟发性克拉伯病的初始症状:1例报告。
IF 2.9 3区 医学 Q2 BEHAVIORAL SCIENCES Pub Date : 2025-12-01 eCollection Date: 2025-01-01 DOI: 10.3389/fnbeh.2025.1741000
Sifen Xie, Zuying Kuang, Mengqiu Pan, Kanghua Zhang, Jinlong Ye, Bo Li, Sheng Luo, Zhanhang Wang

[This corrects the article DOI: 10.3389/fnbeh.2025.1564676.].

[这更正了文章DOI: 10.3389/fnbeh.2025.1564676.]。
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引用次数: 0
Exploring the impact of acute solvent exposure on larval zebrafish behaviour. 探讨急性溶剂暴露对斑马鱼幼虫行为的影响。
IF 2.9 3区 医学 Q2 BEHAVIORAL SCIENCES Pub Date : 2025-11-28 eCollection Date: 2025-01-01 DOI: 10.3389/fnbeh.2025.1717998
Ethan V Hagen, Matthew M M Harper, Yanbo Zhang, Trevor J Hamilton

Zebrafish (Danio rerio) are commonly used to test the impact of pharmacological and toxicological compounds. Larval zebrafish are extensively used because of high throughput procedures allowing simultaneous behavioural measurement in 24-, 48-, or 96-well plates. Often solvents are used as a vehicle for poorly soluble or insoluble compounds, however, the impact of dimethyl sulfoxide (DMSO), methanol, and ethanol after acute administration is not well characterized. Here we investigated the impact of 30-min exposures of DMSO, methanol, and ethanol (0.01%, 0.1%, and 1.0% vol/vol) on 5-day old larval zebrafish locomotion and startle responses. We found no effect of DMSO on distance moved and thigmotaxis in a spontaneous swimming test, and no effect on dark-, light-, or tap-startle responses compared to controls. Methanol and ethanol, both at 1.0% increased the distance moved, and ethanol decreased the dark startle response at 1.0%. Neither ethanol nor methanol had any impact on time in thigmotaxis zone, light- or tap-startle responses. Results from this study suggest that with acute exposure to experimental compounds requiring a solvent, the least impact on behaviour would occur with DMSO, followed by methanol, then ethanol.

斑马鱼(Danio rerio)通常用于测试药理学和毒理学化合物的影响。幼斑马鱼被广泛使用,因为高通量程序允许在24孔、48孔或96孔板中同时进行行为测量。通常溶剂被用作难溶性或不溶性化合物的载体,然而,急性给药后二甲亚砜(DMSO)、甲醇和乙醇的影响并没有很好的表征。在这里,我们研究了暴露于DMSO、甲醇和乙醇(0.01%、0.1%和1.0% vol/vol) 30分钟对5日龄斑马鱼幼虫运动和惊吓反应的影响。在自发游泳试验中,我们发现DMSO对移动距离和移动性没有影响,与对照组相比,对黑暗、光线或轻拍惊吓反应没有影响。1.0%的甲醇和乙醇增加了小鼠移动的距离,1.0%的乙醇降低了小鼠的暗惊反应。乙醇和甲醇对趋动区的时间、光或轻击惊吓反应都没有影响。这项研究的结果表明,在急性暴露于需要溶剂的实验化合物时,DMSO对行为的影响最小,其次是甲醇,然后是乙醇。
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引用次数: 0
Dynamic duos: learning to care as a pair in the biparental prairie vole (Microtus ochrogaster). 动态的二人组:在双亲双亲的草原田鼠(Microtus ochrogaster)中学习作为一对来照顾。
IF 2.9 3区 医学 Q2 BEHAVIORAL SCIENCES Pub Date : 2025-11-26 eCollection Date: 2025-01-01 DOI: 10.3389/fnbeh.2025.1698616
Taylor D Hinton, Rebecca E Waugh, Per B Sederberg, Jessica J Connelly, Allison M Perkeybile

Introduction: A growing body of evidence shows that paternal care has long-lasting impacts on the social behavior of offspring, both in humans and other mammalian biparental species. However, fatherhood has historically been understudied and the dynamics of parental care adjustments based on their partner's behavior remain unclear. This study investigates how individuals adjust parenting behavior based on their experience as part of a parenting dyad in the biparental prairie vole (Microtus ochrogaster).

Methods: We investigated how prairie voles learn to be parents by observing how their parental care effort changes over two consecutive litters. The first litter represents a naive context while the second litter represents an experienced context.

Results: On average, dyads provided 9% more care in the naive context than in the experienced context. Experienced mothers, as a group, tended to reduce care significantly, while experienced fathers did not. By comparing the correlation between mother and father care in the naive versus experienced contexts, we found that parental care became more negatively correlated following experience. Finally, we investigated whether the difference in the amount of care provided by each parent in the dyad in the naive context drives the observed changes in experienced parental behavior, and found that these differences significantly predict the likelihood of reducing or increasing parental care effort in the experienced context for both the male and female partner.

Conclusion: Our results indicate that individual care behavior is adjusted based on the parenting effort of the dyadic partner. When only group-wise analyses are conducted, it appears that only mothers reduce care based on experience. However, through a dyadic-based analysis, we find that a larger difference in care between the two parents in the naive context corresponds to greater shifts in care by both parents in the experienced context. In sum, two patterns emerge in experienced parents that appear to improve parental care efficiency: (1) parents take on a more compensatory pattern of caregiving over time and (2) are able to adapt to initial differences in care such that investments in care become more balanced between mothers and fathers over time.

越来越多的证据表明,在人类和其他双亲本哺乳动物物种中,父系抚育对后代的社会行为具有持久的影响。然而,历史上对父亲身份的研究一直不够充分,基于伴侣行为的父母照顾调整的动态仍不清楚。本研究调查了双亲草原田鼠(Microtus ochrogaster)中个体如何根据其作为双亲双亲双亲双亲的一部分的经验调整育儿行为。方法:通过观察连续两胎草原田鼠亲代照顾力度的变化,研究草原田鼠如何学习成为父母。第一窝代表一个幼稚的环境,而第二窝代表一个有经验的环境。结果:平均而言,二人组在幼稚情境下比在有经验情境下多提供9%的照顾。作为一个群体,经验丰富的母亲往往会显著减少照顾,而经验丰富的父亲则不会。通过比较幼稚情境和经验情境中父母照顾的相关关系,我们发现父母照顾在经历后变得更加负相关。最后,我们调查了双亲在幼稚情境中所提供的照顾量的差异是否驱动了观察到的有经验的父母行为的变化,并发现这些差异显著地预测了在有经验的情境中男性和女性伴侣减少或增加父母照顾努力的可能性。结论:本研究结果表明,个体的照顾行为是根据二元伴侣的养育努力而调整的。当只进行群体分析时,似乎只有母亲根据经验减少照顾。然而,通过二元分析,我们发现父母双方在幼稚情境下的照顾差异越大,父母双方在经验情境下的照顾变化也越大。总之,有经验的父母出现了两种模式,似乎可以提高父母的照顾效率:(1)随着时间的推移,父母采取了一种更具补偿性的照顾模式;(2)能够适应最初的照顾差异,使母亲和父亲之间的照顾投资随着时间的推移变得更加平衡。
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引用次数: 0
Early-life pain alters excitability of corticotropin-releasing factor-expressing neurons in the central amygdala and stress-induced hypersensitivity during adolescence. 早期生活中的疼痛改变了杏仁核中央促肾上腺皮质激素释放因子表达神经元的兴奋性和青春期应激性超敏反应。
IF 2.9 3区 医学 Q2 BEHAVIORAL SCIENCES Pub Date : 2025-11-26 eCollection Date: 2025-01-01 DOI: 10.3389/fnbeh.2025.1653346
Megan Tomasch, Emma Naess, Skyler McComas, Michael A Burman

Introduction: Neonatal intensive care units (NICUs) provide life-saving care for preterm and sick neonates, but many medical procedures are painful and stress-inducing. Even a routine NICU procedure, such as the "heel lancing" blood-draw procedure, is an acutely painful, repetitive manipulation that has lasting negative impacts on pain perception and anxiety responses. The intersection of nociception and negative affect occurs in a brain region called the central nucleus of the amygdala (CeA), and neurons expressing corticotropin-releasing factor (CRF) have been implicated in studies of both anxiety and pain.

Methods: Using a two-hit model of trauma-induced pain vulnerability-where repetitive needle prickings occur during the first week of life ("our NICU model"), followed by a second stressor (e.g., fear conditioning) during adolescence-our lab has observed a mechanical hypersensitivity in rats that endured our NICU model that manifests only after fear conditioning. We have also observed changes to expression and activation of CeA-CRF neurons after the NICU-like experience with an acute increase followed by a lasting reduction in the number of CRF cells in the right CeA of adolescent male rats. However, the relationship between these changes and the observed behavioral outcomes remains unclear, as does the function of the remaining CRF cell population. We hypothesize that the remaining population of CRF-expressing CeA neurons are functionally altered by early life pain and stress and primed to respond more readily, such that vulnerability to stress-induced hypersensitivity is increased.

Results: Through chemogenetic inhibition of the amygdala, or specifically CeA-CRF neurons, we demonstrate that development of stress-induced mechanical hypersensitivity after our NICU model is completely reversed through silencing the amygdala. Inhibiting only CeA-CRF neurons during fear conditioning led to a partial reversal of the hypersensitivity, suggesting that other populations of cells also play critical roles. Nevertheless, we demonstrate that the NICU-like experience results in a lasting hyperexcitability of CeA-CRF neurons during adolescence, confirming that this population is affected by the early life manipulations.

Discussion: In all, this study suggests that CeA-CRF neurons may have pro-nociceptive properties that are exacerbated by early life pain and result in maladaptive responding to subsequent traumatic events.

新生儿重症监护病房(NICUs)为早产儿和生病的新生儿提供挽救生命的护理,但许多医疗程序是痛苦和压力诱导的。即使是常规的新生儿重症监护室手术,如“脚跟穿刺”抽血手术,也是一种非常痛苦的重复性操作,对疼痛感知和焦虑反应有持久的负面影响。痛觉和负面情绪的交集发生在一个叫做杏仁核中央核(CeA)的大脑区域,表达促肾上腺皮质激素释放因子(CRF)的神经元在焦虑和疼痛的研究中都有牵连。方法:使用创伤性疼痛易感的两击模型-在生命的第一周(“我们的新生儿重症监护病房模型”)重复针刺,随后在青春期出现第二次压力源(例如恐惧条件反射)-我们的实验室观察到,在我们的新生儿重症监护病房模型中,只在恐惧条件反射后才表现出机械过敏。我们还观察到在nicu样经历后CeA-CRF神经元的表达和激活的变化,青春期雄性大鼠右侧CeA中CRF细胞的数量急剧增加,随后持续减少。然而,这些变化与观察到的行为结果之间的关系尚不清楚,剩余的CRF细胞群的功能也不清楚。我们假设剩余的表达crf的CeA神经元群体在功能上被早期生活中的疼痛和压力所改变,并且更容易做出反应,从而增加了对压力诱导的超敏反应的脆弱性。结果:通过对杏仁核,特别是CeA-CRF神经元的化学发生抑制,我们证明了通过沉默杏仁核,NICU模型后应激诱导的机械超敏反应的发展完全逆转。在恐惧条件反射过程中,仅抑制CeA-CRF神经元导致超敏反应的部分逆转,这表明其他细胞群也起着关键作用。然而,我们证明了类似新生儿重症监护病房的经历导致青少年时期CeA-CRF神经元的持续高兴奋性,证实了这一人群受到早期生活操作的影响。讨论:总之,这项研究表明,CeA-CRF神经元可能具有前伤害性,这种特性会因早期生活中的疼痛而加剧,并导致对后续创伤事件的适应不良反应。
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引用次数: 0
Editorial: Motivation seen through the kaleidoscope of multi-disciplinarity and multi-scales: towards the emergence of new paradigms and perspectives favored by crossed looks. 编辑:从多学科和多尺度的万花筒中看到的动机:走向交叉视角青睐的新范式和新视角的出现。
IF 2.9 3区 医学 Q2 BEHAVIORAL SCIENCES Pub Date : 2025-11-20 eCollection Date: 2025-01-01 DOI: 10.3389/fnbeh.2025.1728916
Bénédicte Terrier, Jackson Cioni Bittencourt, Sandrine Parrot
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引用次数: 0
期刊
Frontiers in Behavioral Neuroscience
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