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Beyond the undermining effect: Extrinsic rewards preserve neural intrinsic reward 超越破坏效应:外在奖励保护神经内在奖励。
IF 2.3 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2026-03-12 Epub Date: 2025-12-13 DOI: 10.1016/j.bbr.2025.115996
Hiroaki Ayabe , Takahiko Koike , Ayumi Yoshioka , Satoshi Izuno , Kanae Ogasawara , Shohei Tsuchimoto , Norihiro Sadato
The Self-Determination Theory posits that extrinsic reward withdrawal often undermines intrinsic motivation. This undermining effect varies according to the reward category (e.g., monetary vs. praise). However, the mechanism underlying this variability remains unclear, partly because previous studies have conceptualized intrinsic motivation as a single construct without distinguishing liking (intrinsic value) from wanting (motivational drive). Failure to make this distinction may obscure the effects of rewards on each component. We hypothesized that extrinsic reward withdrawal would differentially affect intrinsic value and motivational drive. To test this hypothesis, we conducted functional magnetic resonance imaging (fMRI) on 54 participants who were randomly assigned to one of three conditions: control (no rewards), monetary reward, or social reward. Participants in the monetary and social reward groups played a stopwatch game twice, first with and then without extrinsic rewards. The control group received no extrinsic rewards during the task. We assessed intrinsic value through fMRI-measured activation of the reward system and motivational drive through voluntary engagement during the task intermission. Intrinsic value, measured by activation in predefined reward-related regions, declined in the control group but was preserved in both extrinsic reward groups after withdrawal. Thus, both monetary and social rewards were associated with preserved intrinsic value. However, intrinsic behavioral motivation declined in the monetary group but was maintained in the social group. These findings suggest that extrinsic reward withdrawal differentially influences intrinsic value and motivational drive across reward categories, thereby clarifying the variability of the undermining effect.
自我决定理论认为,外在奖励的退缩往往会破坏内在动机。这种破坏效应因奖励类别而异(例如,金钱vs.赞美)。然而,这种差异背后的机制尚不清楚,部分原因是先前的研究将内在动机概念化为单一结构,没有区分喜欢(内在价值)和想要(动机驱动)。如果不能区分这一点,奖励对每个组成部分的影响就会变得模糊。我们假设外在奖励退缩会对内在价值和动机驱动产生不同的影响。为了验证这一假设,我们对54名参与者进行了功能性磁共振成像(fMRI),他们被随机分配到三种情况中的一种:控制(没有奖励)、金钱奖励或社会奖励。金钱奖励组和社会奖励组的参与者玩了两次秒表游戏,第一次有外部奖励,然后没有。对照组在任务过程中没有获得任何外部奖励。我们通过fmri测量奖励系统的激活和任务间歇期间自愿参与的动机驱动来评估内在价值。内在价值,通过预先定义的奖励相关区域的激活来测量,在对照组中下降,但在退出后,两个外在奖励组都保持不变。因此,货币和社会奖励都与保留的内在价值有关。然而,内在行为动机在货币组中有所下降,而在社会组中则保持不变。这些研究结果表明,外在奖励退缩对不同奖励类别的内在价值和动机驱动的影响是不同的,从而阐明了破坏效应的可变性。
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引用次数: 0
Combining network pharmacology, machine learning, molecular docking, molecular simulation dynamics and experimental validation to explore the mechanism of Zhenwu decoction in treating major depression through TNF-α pathways 结合网络药理学、机器学习、分子对接、分子模拟动力学、实验验证等方法,探讨真五汤通过TNF-α通路治疗重度抑郁症的机制。
IF 2.3 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2026-03-12 Epub Date: 2025-12-23 DOI: 10.1016/j.bbr.2025.115997
Xinyu Zhou , Yan Gao , Sashuang Liu , Yijing Zhao , Zhen Wang , Dexiang Liu

Background

Major depressive disorder (MDD) is a severe psychophysiological condition characterized by cognitive decline, low energy, weight loss, insomnia, and increased suicide risk, posing a significant burden on global health. Zhenwu decoction (ZWD), a traditional Chinese medicine, has shown therapeutic potential in alleviating MDD symptoms. However, its complex composition has limited the understanding of its underlying pharmacological mechanisms. This study aimed to explore the antidepressant mechanisms of ZWD in the treatment of MDD.

Methods

Active compounds and potential targets of ZWD were identified through database screening and network pharmacology analysis. These targets were intersected with MDD-related genes to construct a protein–protein interaction network. Core targets were further refined using random forest algorithms. Molecular docking and molecular dynamics simulations were employed to evaluate the binding affinity and stability between key compounds and core targets. Experimental validation was conducted in a lipopolysaccharide (LPS)-induced mice model of depression using behavioral testing, measurement of inflammatory cytokines, and gene expression analysis.

Results

Network pharmacology and machine learning identified TNF-α signaling as key pathways in the antidepressant effects of ZWD. Enrichment analysis highlighted the involvement of Lipid and atherosclerosis, the IL-17 signaling pathway. Core targets, including PPARG, F10, AR, TNF, PIK3CG, ADH1C, and GABRA6, were predicted to mediate its effects. Molecular docking and dynamics simulations confirmed strong binding of ZWD components, especially kaempferol, to TNF-α, inhibiting its expression. In vivo, ZWD improved anxiety/depressive-like behaviors in LPS-treated mice, evidenced by better performance in the behavioral tests. ZWD also reduced neuroinflammation, with decreased Tnf-α levels, and reduced IBA-1 and GFAP staining, indicating reduced microglial and astrocyte activation. These results suggest that ZWD alleviates depression through modulation of TNF-α–mediated inflammation.

Conclusions

These findings suggest that ZWD exerts antidepressant effects primarily by modulating TNF-α–mediated inflammatory pathways, providing a comprehensive molecular and experimental framework supporting its clinical potential in MDD treatment.
背景:重度抑郁症(MDD)是一种以认知能力下降、精力不足、体重减轻、失眠和自杀风险增加为特征的严重心理生理疾病,对全球健康造成了重大负担。中药真武汤(ZWD)在缓解重度抑郁症(MDD)症状方面显示出治疗潜力。然而,其复杂的组成限制了对其潜在药理机制的理解。本研究旨在探讨ZWD治疗重度抑郁症的抗抑郁机制。方法:通过数据库筛选和网络药理学分析,鉴定ZWD的活性成分和潜在靶点。这些靶点与mdd相关基因相交,构建蛋白-蛋白相互作用网络。利用随机森林算法进一步细化核心目标。通过分子对接和分子动力学模拟来评估关键化合物与核心靶点之间的结合亲和力和稳定性。在脂多糖(LPS)诱导的抑郁症小鼠模型中,通过行为测试、炎症细胞因子测量和基因表达分析进行了实验验证。结果:网络药理学和机器学习发现TNF-α信号通路是ZWD抗抑郁作用的关键途径。富集分析强调了脂质和动脉粥样硬化,IL-17信号通路的参与。核心靶点,包括PPARG、F10、AR、TNF、PIK3CG、ADH1C和GABRA6,预计介导其作用。分子对接和动力学模拟证实了ZWD成分,特别是山奈酚与TNF-α的强结合,抑制其表达。在体内,ZWD改善了lps治疗小鼠的焦虑/抑郁样行为,在行为测试中表现更好。ZWD还能减轻神经炎症,降低Tnf-α水平,降低IBA-1和GFAP染色,表明小胶质细胞和星形胶质细胞活化减少。上述结果提示,ZWD通过调节TNF-α-介导的炎症来缓解抑郁。结论:这些研究结果表明,ZWD主要通过调节TNF-α-介导的炎症途径发挥抗抑郁作用,为其治疗重度抑郁症的临床潜力提供了全面的分子和实验框架。
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引用次数: 0
Chronic administration of berberine attenuates depressive-like behavior in rats subjected to chronic unpredictable mild stress combined with ACTH treatment: Role of nitrergic system 慢性给药小檗碱减轻大鼠遭受慢性不可预测的轻度应激联合ACTH治疗的抑郁样行为:氮能系统的作用。
IF 2.3 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2026-03-12 Epub Date: 2025-12-20 DOI: 10.1016/j.bbr.2025.116006
Sharvari Deshmukh , Biru B. Dudhabhate , Dipak K. Sahare , Dadasaheb M. Kokare , Yashashree A. Gadhikar
Major depressive disorder (MDD) remains a significant clinical concern because of its poor response to conventional antidepressants. Berberine, an isoquinoline alkaloid of natural origin has shown promising antidepressant-like effects in preclinical models. However, the mechanism by which berberine ameliorates depressive-like behavior has not been clearly studied. Herein, we examined the effect of berberine on depression induced by chronic unpredictable mild stress (CUMS) combined with adrenocorticotropic hormone (ACTH) treatment in rats and explored the role of the nitrergic system in its mechanism. The CUMS (42 days) with ACTH (14 days) -treated rats showed decreased sucrose preference, percentage of time spent in the central area of open field tests, exploration towards the novel object in the novel object recognition test, and increased immobility time in the forced swim test. There was increased neuronal nitric oxide synthase (nNOS) immunoreactivity in the paraventricular nucleus of hypothalamus (PVN), serum corticosterone level, and reduced dopamine and serotonin levels of the hippocampus in the CUMS + ACTH-treated rats. The chronic intraperitoneal (i.p.) administration of berberine (5 mg/kg; i.p.) for 14 days to the CUMS + ACTH-treated rats reversed all these parameters. Furthermore, the administration of sodium nitroprusside (SNP; 1 mg/kg) prior to the berberine treatment in CUMS + ACTH-treated rats blocked its positive effect. The findings suggest that berberine treatment may exert its antidepressant-like and memory-enhancing effects, at least in part, by attenuating hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, potentially through the involvement of nitrergic signaling.
重度抑郁障碍(MDD)仍然是一个重要的临床问题,因为它对传统抗抑郁药物的反应很差。小檗碱是一种天然来源的异喹啉生物碱,在临床前模型中显示出有希望的抗抑郁样作用。然而,小檗碱改善抑郁样行为的机制尚未得到明确的研究。本研究研究了小檗碱对慢性不可预测轻度应激(CUMS)联合促肾上腺皮质激素(ACTH)治疗大鼠抑郁症的影响,并探讨了氮能系统在其机制中的作用。经ACTH(14天)处理的CUMS(42天)大鼠对蔗糖的偏好降低,在空地试验中停留在中心区域的时间百分比降低,在新物体识别试验中探索新物体的时间百分比降低,在强迫游泳试验中静止不动的时间增加。CUMS + acth处理大鼠下丘脑室旁核(PVN)神经元一氧化氮合酶(nNOS)免疫反应性升高,血清皮质酮水平升高,海马多巴胺和血清羟色胺水平降低。慢性腹腔注射黄连素(5mg/kg; i.p)给CUMS + acth治疗的大鼠14天,逆转了所有这些参数。此外,在CUMS + acth治疗大鼠小檗碱治疗前给予硝普钠(SNP; 1mg/kg; i.p.)阻断了其积极作用。研究结果表明,小檗碱治疗可能发挥其抗抑郁和增强记忆的作用,至少部分是通过减少下丘脑-垂体-肾上腺(HPA)轴的过度活跃,可能通过参与氮能信号传导。
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引用次数: 0
Effects of Chronic Oxycodone Administration on the Rat's Hippocampus: Behavioral and histopathological studies. 慢性羟考酮给药对大鼠海马的影响:行为学和组织病理学研究。
IF 2.3 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2026-03-10 DOI: 10.1016/j.bbr.2026.116140
Erfan Motalebzadeh, Ali Charmchi, Mahdi Soroosh, Seyed Shahab Gazi Mirsaeed, Amirreza Beirami, Maral Hasanzadeh, Mahdi Tizro, Reza Heidari, Amirmahdi Zeynalzadeh, Mohsen Chamanara, Abbas Aliaghaei, Meysam Hassani Moghaddam

Oxycodone is a potent opioid frequently prescribed for pain management and is associated with a high tendency for abuse. This study investigated the impact of chronic oxycodone use on hippocampal structure and function in rats. Twenty-four adult male albino rats were randomly divided into a control group (n=12) and an oxycodone-treated group (n=12), receiving oral oxycodone (15mg/kg) daily for 30 days. Behavioral tests included the Y-maze, shuttle box, elevated plus maze, tail suspension tests, Morris water maze and Barnes test. Immunohistochemical analysis was performed to evaluate the expression of Ki67 and caspase-3 in the hippocampus. Glial morphology and distribution were assessed using GFAP and Iba-1 antibodies, and the spatial distribution of neurons was analyzed using Voronoi tessellation. Chronic administration of oxycodone significantly reduced spatial working memory and increased depressive-like behavior. No significant changes were observed in anxiety-like behavior, spatial memory or long-term memory. Immunohistochemical analysis revealed a significant decrease in Ki67 expression and an increase in caspase-3 expression in the oxycodone-treated group. Oxycodone administration also led to an increase in astrogliosis, although astrocyte morphology was not significantly altered. Neuronal distribution analysis of the hippocampus in the oxycodone group showed a more regular distribution pattern in the pyramidal layer, with a significant increase in the proportion of larger Voronoi polygons. Chronic oxycodone administration reduces hippocampal neurogenesis, increases apoptotic activity, and affects neuronal distribution, resulting in behavioral alterations in rats. These findings highlight oxycodone's broader neurobiological impacts and the significance of tailored therapeutic techniques to reduce its effects on brain function.

羟考酮是一种有效的阿片类药物,经常用于疼痛管理,并与滥用的高倾向有关。本研究探讨了长期使用羟考酮对大鼠海马结构和功能的影响。将24只成年雄性白化大鼠随机分为对照组(n=12)和羟考酮治疗组(n=12),每天口服羟考酮(15mg/kg),连续30 d。行为学测试包括y型迷宫、穿梭箱、高架+迷宫、悬尾测试、Morris水迷宫和Barnes测试。免疫组化分析海马组织中Ki67和caspase-3的表达。使用GFAP和Iba-1抗体评估神经胶质形态和分布,使用Voronoi镶嵌分析神经元的空间分布。长期服用羟考酮可显著降低空间工作记忆,增加抑郁样行为。在焦虑类行为、空间记忆或长期记忆方面没有观察到明显的变化。免疫组化分析显示,羟考酮组Ki67表达显著降低,caspase-3表达显著升高。羟考酮也导致星形胶质细胞增多,尽管星形胶质细胞形态没有明显改变。羟考酮组海马神经元分布分析显示,锥体层的分布更为规则,较大Voronoi多边形的比例明显增加。慢性羟考酮可减少大鼠海马神经发生,增加凋亡活性,影响神经元分布,导致行为改变。这些发现强调了羟考酮更广泛的神经生物学影响和定制治疗技术的重要性,以减少其对脑功能的影响。
{"title":"Effects of Chronic Oxycodone Administration on the Rat's Hippocampus: Behavioral and histopathological studies.","authors":"Erfan Motalebzadeh, Ali Charmchi, Mahdi Soroosh, Seyed Shahab Gazi Mirsaeed, Amirreza Beirami, Maral Hasanzadeh, Mahdi Tizro, Reza Heidari, Amirmahdi Zeynalzadeh, Mohsen Chamanara, Abbas Aliaghaei, Meysam Hassani Moghaddam","doi":"10.1016/j.bbr.2026.116140","DOIUrl":"https://doi.org/10.1016/j.bbr.2026.116140","url":null,"abstract":"<p><p>Oxycodone is a potent opioid frequently prescribed for pain management and is associated with a high tendency for abuse. This study investigated the impact of chronic oxycodone use on hippocampal structure and function in rats. Twenty-four adult male albino rats were randomly divided into a control group (n=12) and an oxycodone-treated group (n=12), receiving oral oxycodone (15mg/kg) daily for 30 days. Behavioral tests included the Y-maze, shuttle box, elevated plus maze, tail suspension tests, Morris water maze and Barnes test. Immunohistochemical analysis was performed to evaluate the expression of Ki67 and caspase-3 in the hippocampus. Glial morphology and distribution were assessed using GFAP and Iba-1 antibodies, and the spatial distribution of neurons was analyzed using Voronoi tessellation. Chronic administration of oxycodone significantly reduced spatial working memory and increased depressive-like behavior. No significant changes were observed in anxiety-like behavior, spatial memory or long-term memory. Immunohistochemical analysis revealed a significant decrease in Ki67 expression and an increase in caspase-3 expression in the oxycodone-treated group. Oxycodone administration also led to an increase in astrogliosis, although astrocyte morphology was not significantly altered. Neuronal distribution analysis of the hippocampus in the oxycodone group showed a more regular distribution pattern in the pyramidal layer, with a significant increase in the proportion of larger Voronoi polygons. Chronic oxycodone administration reduces hippocampal neurogenesis, increases apoptotic activity, and affects neuronal distribution, resulting in behavioral alterations in rats. These findings highlight oxycodone's broader neurobiological impacts and the significance of tailored therapeutic techniques to reduce its effects on brain function.</p>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":" ","pages":"116140"},"PeriodicalIF":2.3,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Resveratrol prevents arsenic-induced depression-like phenotypes via modulation of BDNF signaling 白藜芦醇通过调节BDNF信号传导阻止砷诱导的抑郁样表型。
IF 2.3 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2026-03-05 Epub Date: 2025-12-09 DOI: 10.1016/j.bbr.2025.115988
Mohaddeseh Kharazmi , Tayyebeh Khalili , Marzieh Dehghan-Shasaltaneh , Abbas Bahari , Mohaddeseh Ebrahimi-Ghiri
Growing evidence suggests that resveratrol possesses neuroprotective properties against arsenic toxicity. This study investigated whether resveratrol could ameliorate arsenic-induced depression-like behaviors in male Naval Medical Research Institute (NMRI) mice and explored potential molecular mechanisms. Mice were exposed to arsenic (50 mg/L in drinking water) for 4 weeks and treated with resveratrol (10 or 20 mg/kg). Behavioral assessments included the hole-board test (HBT) for exploratory behavior, and the sucrose splash test (SST), tail suspension test (TST), and forced swim test (FST) for depression-like behaviors. The mRNA levels of Bdnf, Creb1, and Dvl1 in the brain were analyzed by qRT-PCR. Arsenic exposure induced significant depression-like behaviors, characterized by decreased grooming in SST and increased immobility in TST and FST. Resveratrol treatment prevented these behavioral alterations and exhibited intrinsic antidepressant effects in naïve mice, with dose-dependent reductions in immobility time (FST) and increased grooming (SST). Notably, resveratrol (20 mg/kg) enhanced rearing frequency in naïve mice and decreased it in the arsenic-treated mice. At the molecular level, arsenic downregulated Bdnf expression, while resveratrol restored its levels. In contrast, no significant changes in Creb1 and Dvl1 expression were observed. These findings indicate that resveratrol mitigates arsenic-induced depression-like behaviors primarily through the modulation of Bdnf-dependent pathways, independent of Creb1 and Dvl1. These results position resveratrol as a potential antidepressant and underscore its therapeutic promise for mood disorders associated with environmental toxicant exposure.
越来越多的证据表明,白藜芦醇具有抗砷毒性的神经保护特性。本研究旨在探讨白藜芦醇是否能改善美国海军医学研究所(Naval Medical Research Institute, NMRI)雄性小鼠砷诱导的抑郁样行为,并探讨可能的分子机制。小鼠暴露于砷(饮用水中50mg/L) 4周,并用白藜芦醇(10或20mg/kg)处理。行为评估包括探索性行为的孔板测试(HBT),以及抑郁样行为的蔗糖飞溅测试(SST)、悬尾测试(TST)和强迫游泳测试(FST)。采用qRT-PCR分析脑内Bdnf、Creb1、Dvl1 mRNA表达水平。砷暴露诱导了显著的抑郁样行为,其特征是SST的修饰减少,TST和FST的不动增加。在naïve小鼠中,白藜芦醇治疗阻止了这些行为改变,并表现出内在的抗抑郁作用,其剂量依赖性地减少了静止时间(FST)和增加了梳洗(SST)。值得注意的是,白藜芦醇(20mg/kg)提高了naïve小鼠的饲养频率,降低了砷处理小鼠的饲养频率。在分子水平上,砷降低了Bdnf的表达,而白藜芦醇则恢复了Bdnf的表达。相比之下,Creb1和Dvl1的表达没有明显变化。这些发现表明,白藜芦醇减轻砷诱导的抑郁样行为主要是通过调节bdnf依赖途径,独立于Creb1和Dvl1。这些结果将白藜芦醇定位为一种潜在的抗抑郁药,并强调了其治疗与环境毒物暴露相关的情绪障碍的前景。
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引用次数: 0
Retraction notice to “Inhibition of glucocorticoid receptors ameliorates hypobaric hypoxia induced memory impairment in rat” [Behav. Brain Res. 240 (2013) 76–86] “抑制糖皮质激素受体可改善低氧缺氧引起的大鼠记忆障碍”的撤回通知[行为]。脑科学进展,2013(4):376 - 386。
IF 2.3 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2026-03-05 Epub Date: 2025-12-09 DOI: 10.1016/j.bbr.2025.115980
Iswar Baitharu , Satya Narayan Deep , Vishal Jain , Dipti Prasad , G. Ilavazhagan
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引用次数: 0
Transmuscular vocal fold injury reduces frequency complexity of rat ultrasonic vocalizations 经肌肉声带损伤可降低大鼠超声发声频率的复杂性。
IF 2.3 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2026-03-05 Epub Date: 2025-12-08 DOI: 10.1016/j.bbr.2025.115989
Marilla Gould , Ryosuke Nakamura , Wenqing Yang , Ryan C. Branski , Aaron M. Johnson
Rapid and precise activation of the laryngeal musculature, particularly the thyroarytenoid (TA), is required for the production of rat ultrasonic vocalizations (USVs). Although the role of the TA in USV production has been established through denervation and excised larynx studies, how TA muscle dysfunction affects USV acoustics remains unknown. This study examined how iatrogenic, transmuscular vocal fold injury influences USV production by comparing acoustic parameters between rats receiving bilateral transmuscular vocal fold injury (including the TA muscle) versus sham surgery. Twenty adult male rats were randomly assigned to injury or sham groups and assessed at 30 or 60 days post-surgery. USVs were recorded at each timepoint (pre- and post-surgery) and analyzed for changes in principal frequency, frequency complexity (standard deviation and sinuosity), power (intensity of the USV), tonality, and duration. Injury significantly decreased USV frequency complexity and reduced the likelihood of producing frequency-modulated vocalizations in both post-surgical time groups. These findings demonstrate that while TA muscle integrity is crucial for frequency modulation, it is not necessary for basic USV production, offering new insights into the biomechanical role of the TA muscle in rat vocalization and laying the groundwork for investigating therapeutic interventions targeting laryngeal muscle function.
快速和精确地激活喉部肌肉组织,特别是类甲状腺肌(TA),是产生大鼠超声发声(usv)所必需的。虽然通过去神经支配和切除喉的研究已经确定了TA在USV产生中的作用,但TA肌肉功能障碍如何影响USV声学仍然未知。本研究通过比较双侧经肌性声带损伤(包括TA肌)和假手术大鼠的声学参数,研究了医源性经肌性声带损伤对USV产生的影响。将20只成年雄性大鼠随机分为损伤组和假手术组,分别于术后30天和60天进行评估。在每个时间点记录USV,并分析主频率、频率复杂度(标准差和弯曲度)、功率(USV强度)、音调和持续时间的变化。损伤显著降低了USV频率的复杂性,并减少了术后两个时间点产生调频发声的可能性。这些发现表明,虽然TA肌的完整性对于频率调制至关重要,但对于基本的USV产生并非必需,这为TA肌在大鼠发声中的生物力学作用提供了新的见解,并为研究针对喉肌功能的治疗干预奠定了基础。
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引用次数: 0
Effects of intranasal oxytocin administration on histophysiology of the hippocampus in maternally separated adolescent male rats 鼻内注射催产素对母分离雄性大鼠海马组织生理学的影响。
IF 2.3 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2026-03-05 Epub Date: 2025-12-08 DOI: 10.1016/j.bbr.2025.115983
Parisa Salehi Najafabadi , Ali Shamsara , Vida Mirzaie , Vahid Sheibani , Mahdiyeh Ahmadi , Sara Joushi , Mohsen Basiri
Astrocytes are one of the glial cells of the nervous system. These cells reach their maximum number in the first two weeks after birth. Therefore, during this period they are sensitive to adverse conditions, including separation from the mother. One of the factors is the stress-modulating hormone oxytocin (OT). Adolescent male Wistar rats were used in this study. Rat pups were subjected to the MS protocol for 180 min per day from postnatal day 1–21 (postnatal day (PND)). Then, from PND 22–34, OT was administered intranasally (2 μg/μl, for 7 days). Behavioral assessments were performed on PND 35–37, we prespecified glial fibrillary acidic protein (GFAP)+ astrocyte density and morphology as the primary outcome, given astrocytes’ active roles in synaptic plasticity, stress regulation, and oxytocin signaling; the neuron degeneration ratio and p38/p-p38 expression were treated as secondary outcomes. MS did not alter locomotion; it increased anxiety-like behavior in the Zero Maze Test (ZMT) (but not in the Open Field Test (OFT)) and elevated olfactory thresholds. MS also increased the degenerated/healthy neuron ratio and p38/p-p38 protein levels, and reduced GFAP+ astrocyte density and process size in hippocampal CA1; OT partly reversed these glial/inflammatory changes without affecting the neuron degeneration ratio. These findings suggest that OT could serve as a therapeutic agent to improve some of the adverse behavioral and histological effects of MS in modern societies.
星形胶质细胞是神经系统的一种胶质细胞。这些细胞在出生后的前两周达到最大数量。因此,在此期间,他们对不利条件很敏感,包括与母亲分离。其中一个因素是压力调节激素催产素(OT)。本研究采用青春期雄性Wistar大鼠。从大鼠出生后第1天至第21天(PND),每天进行180分钟的MS治疗。然后,从PND 22至34,经鼻给药OT (2μg/μl, 7 d)。考虑到星形胶质细胞在突触可塑性、应激调节和催产素信号传导方面的积极作用,我们预先指定了胶质纤维酸性蛋白(GFAP)+星形胶质细胞密度和形态作为主要结果;神经元变性率和p38/p-p38表达作为次要结局。MS不改变运动;它在零迷宫测试(ZMT)中增加了焦虑样行为(但在开放场地测试(OFT)中没有),并提高了嗅觉阈值。MS还增加了退化/健康神经元比例和p38/p-p38蛋白水平,降低了海马CA1中GFAP+星形胶质细胞密度和过程大小;OT部分逆转了这些胶质/炎症变化,而不影响神经元变性率。这些发现表明,在现代社会中,OT可以作为一种治疗药物来改善MS的一些不良行为和组织学影响。
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引用次数: 0
Symptom-specific neural circuits and corresponding transcriptomic profiles in depression 抑郁症的症状特异性神经回路和相应的转录组谱。
IF 2.3 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2026-03-05 Epub Date: 2025-11-25 DOI: 10.1016/j.bbr.2025.115966
Jiang Wang , Chengfeng Chen , Xuanyu Zhang , Shiying Wang , Ru Hao , Yubing Xu , Nan Fang , Huina Teng , Bin Zhang

Background

Depression is a clinically heterogeneous disorder with symptom-specific neural correlates. However, systematic mapping of brain networks underlying individual symptoms remains limited, hindering deeper neurobiological understanding.

Methods

This study used the functional connectivity network mapping method to explore neural circuits associated with specific depressive symptoms, integrating resting-state functional magnetic resonance imaging data from multiple studies. Additionally, transcriptomic analysis was performed to examine the relationship between symptom-specific functional connectivity networks and gene expression.

Results

This study identified distinct neural circuits associated with specific depressive symptoms. Damage networks related to anxiety, cognitive impairment, and rumination were primarily localized within the limbic network or default mode network, while anhedonia and suicide ideation/attempt were mainly linked to the visual network. Transcriptomic analysis further identified genes linked to these networks, highlighting synaptic function, neural plasticity, and neurotransmission as key processes driven by gene expression underlying depressive symptoms. Functional enrichment analysis also revealed distinct neurobiological profiles for different symptoms, including specific immune-related processes for cognitive impairment and neurodevelopmental features for sleep disturbance.

Conclusions

This study identified neural circuits associated with specific depressive symptoms and their associated brain gene expression. The findings revealed symptom-specific damage networks, highlighting key biological processes including synaptic signaling, neural plasticity, and neurotransmission. Additionally, distinct neurobiological features were observed, including immune-related processes linked to cognitive impairment and neurodevelopmental characteristics related to sleep disturbance. These findings may provide new insights into the neurobiological mechanisms of depression.
背景:抑郁症是一种具有症状特异性神经相关的临床异质性疾病。然而,对个体症状背后的大脑网络的系统映射仍然有限,阻碍了更深入的神经生物学理解。方法:结合多项研究的静息状态功能磁共振成像数据,采用功能连接网络映射方法探索与特定抑郁症状相关的神经回路。此外,进行转录组学分析以检查症状特异性功能连接网络与基因表达之间的关系。结果:本研究确定了与特定抑郁症状相关的不同神经回路。与焦虑、认知障碍和反刍相关的损伤网络主要位于边缘网络或默认模式网络中,而快感缺乏和自杀意念/企图主要与视觉网络有关。转录组学分析进一步确定了与这些网络相关的基因,强调突触功能、神经可塑性和神经传递是抑郁症状背后基因表达驱动的关键过程。功能富集分析还揭示了不同症状的不同神经生物学特征,包括认知障碍的特异性免疫相关过程和睡眠障碍的神经发育特征。结论:本研究确定了与特定抑郁症状相关的神经回路及其相关的脑基因表达。研究结果揭示了症状特异性损伤网络,突出了包括突触信号、神经可塑性和神经传递在内的关键生物学过程。此外,还观察到不同的神经生物学特征,包括与认知障碍相关的免疫相关过程和与睡眠障碍相关的神经发育特征。这些发现可能为抑郁症的神经生物学机制提供新的见解。
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引用次数: 0
Advanced age and lipopolysaccharide influence behavioral and neurodegenerative features in LRRK2 G2019S knock-in mice 高龄和脂多糖影响LRRK2 G2019S敲入小鼠的行为和神经退行性特征。
IF 2.3 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2026-03-05 Epub Date: 2025-12-03 DOI: 10.1016/j.bbr.2025.115970
Anuroopa Dinesh, Teresa Fortin, Hongyu Sun, Shawn Hayley
Parkinson’s disease (PD) is a progressive neurodegenerative disease thought to arise from the collective impact of advancing age, genetic vulnerabilities and possibly exposure to environmental toxicants. The LRRK2 point mutation, G2019S, is the most common genetic link with PD and has been reported to have age-dependent effects in rodents, as well as being linked to neuroinflammatory processes. Accordingly, the objective of the current study was to elucidate the interactive effects of advanced age and activation of the immune system using the bacterial endotoxin, lipopolysaccharide (LPS), in G2019S knockin mice and their wild type littermates. Adult young (3–4 months) and aged (9–12 months) mice were administered five intraperitoneal injections of 250 ug/kg of LPS (or saline) every alternate day. Significant interactions between age, genotype and injection were evident across several behavioral outcomes. In fact, the aged G2019S mice were more vulnerable to the LPS injections in terms of the sickness response, deficits in nest building behaviors, weight loss, along with protracted reductions in home cage motor activity. These mice also exhibited alterations of SNc inflammatory microglia proteins (WAVE2 and CXCR1) and had the greatest loss of substantia nigra dopamine neurons, which is consistent with a PD-like phenotype. Taken together, our data suggest that the LRRK2 G2019S mutation might be a general regulator of aging and inflammatory processes that are important for neurodegeneration, together with motor and non-motor symptoms.
帕金森病(PD)是一种进行性神经退行性疾病,被认为是由年龄增长、遗传脆弱性和可能暴露于环境毒物的共同影响引起的。LRRK2点突变G2019S是与PD最常见的遗传联系,据报道,在啮齿动物中具有年龄依赖性影响,并与神经炎症过程有关。因此,本研究的目的是阐明高龄和利用细菌内毒素脂多糖(LPS)激活免疫系统对G2019S敲入小鼠及其野生型幼崽的相互作用。将成年幼龄(3-4个月)和成年(9-12个月)小鼠腹腔注射LPS(或生理盐水)250mg/kg,每隔一天5次。在几个行为结果中,年龄、基因型和注射之间的显著相互作用是显而易见的。事实上,年老的G2019S小鼠在疾病反应、筑巢行为缺陷、体重减轻以及家庭笼子运动活动的长期减少方面更容易受到LPS注射的影响。这些小鼠还表现出SNc炎性小胶质细胞蛋白(WAVE2和CXCR1)的改变,并且黑质多巴胺神经元的损失最大,这与pd样表型一致。综上所述,我们的数据表明,LRRK2 G2019S突变可能是衰老和炎症过程的一般调节剂,这些过程对神经退行性变以及运动和非运动症状都很重要。
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Behavioural Brain Research
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