Behavioural Brain Research最新文献_第2页

Sex differences in exploratory behavior of rats successfully performing the object-in-place recognition memory test 成功完成原地物体识别记忆测试的大鼠探索行为的性别差异

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2024-10-22 DOI: 10.1016/j.bbr.2024.115303

Male and female rodents display unique search strategies when exploring new and familiar environments. Sex differences are well-documented in the literature and may be observed in tasks that rely on spontaneous exploration (e.g., recognition memory tests). Therefore, we assessed patterns of male and female rat behavior in the object-in-place (OiP) test, a common recognition memory paradigm involving object-location associations. Twelve male and 12 female adult Long Evans rats were tested four times in the 1-h OiP test and exploratory behaviors were compared during habituation, sample, and test phases. Results revealed that females moved faster and farther than males, showed increased immobility frequency and reduced immobility duration, reduced outer zone mobility duration, and increased inner zone entrances, compared to males during habituations. During sample phases, female rats moved faster than males, displayed reduced immobility frequency in the inner zone, and demonstrated consistent distance travelled across repeated sessions; conversely, male rats moved less in later sessions and exhibited increased mobility frequency in the outer zone. Analyses comparing test phase behavior revealed females continued to move faster than males; however, no other sex differences were observed. These findings are consistent with previous literature highlighting unique sex differences in explorative behaviors during recognition testing. Sex differences in locomotion and mobility state behaviors may be more indicative of individual motivation and search strategy between the sexes and less indicative of recognition memory.

雄性和雌性啮齿动物在探索新环境和熟悉环境时会表现出独特的搜索策略。性别差异在文献中有大量记载，在依赖自发探索的任务（如识别记忆测试）中也可能观察到性别差异。因此，我们评估了雌雄大鼠在 "就地取物"（OiP）测试中的行为模式。我们对 12 只雄性和 12 只雌性成年长伊文大鼠进行了四次为期 1 小时的 OiP 测试，并比较了它们在习惯、取样和测试阶段的探索行为。结果显示，与雄性大鼠相比，雌性大鼠在习惯阶段的移动速度更快、距离更远，固定频率增加、固定时间缩短，外区移动时间缩短、内区进入增加。在样本阶段，雌性大鼠比雄性大鼠移动得更快，在内侧区域的不动频率降低，并且在重复训练中表现出一致的移动距离；相反，雄性大鼠在后期训练中移动得较少，并且在外侧区域表现出更高的移动频率。对测试阶段行为的比较分析表明，雌性大鼠的移动速度仍然快于雄性大鼠，但没有观察到其他性别差异。这些发现与之前的文献一致，都强调了识别测试期间探索行为的独特性别差异。运动和移动状态行为的性别差异可能更多地表现在性别间的个体动机和搜索策略上，而不是识别记忆上。

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引用次数: 0

A new 2-hit model combining serine racemase deletion and maternal separation displays behavioral and cognitive deficits associated with schizophrenia 一种结合了丝氨酸消旋酶缺失和母体分离的新型双击模型显示出与精神分裂症相关的行为和认知障碍。

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2024-10-21 DOI: 10.1016/j.bbr.2024.115301

Schizophrenia (SCZ) is a multifactorial psychotic disorder characterized by positive and negative symptoms as well as cognitive impairments. To advance the current treatments, it is important to improve animal models by considering the multifactorial etiology, thus by combining different risk factors. The objective of our study was to explore in a new mouse model, the impact of genetic deletion of serine racemase (genetic vulnerability) combined with an early stress factor induced by maternal separation (early environmental exposure) in the context of SCZ development. The face validity of the model was assessed through a wide range of behavioral experiments. The 2-hit mice displayed an increased locomotor activity mimicking positive symptoms, working memory impairment, cognitive deficits and recognition memory alterations, which could reflect neophobia. This new multifactorial model therefore presents an interesting phenotype for modelling animal model with partial behavioral and cognitive deficits associated with SCZ.

精神分裂症（SCZ）是一种多因素精神病，以阳性和阴性症状以及认知障碍为特征。为了推进当前的治疗方法，必须通过考虑多因素病因，从而结合不同的风险因素来改进动物模型。我们研究的目的是在一个新的小鼠模型中探讨丝氨酸消旋酶基因缺失（遗传易感性）与母体分离诱导的早期应激因素（早期环境暴露）对SCZ发展的影响。该模型的表面有效性通过一系列行为实验进行了评估。受到2次打击的小鼠表现出模仿阳性症状的运动活动增加、工作记忆受损、认知障碍和识别记忆改变，这可能反映了恐新症。因此，这种新的多因素模型为模拟与 SCZ 相关的部分行为和认知障碍的动物模型提供了一种有趣的表型。

引用次数: 0

The dopamine transporter inhibition using GBR 12909 as a novel pharmacological tool to assess bipolar disorder-like neurobehavioral phenotypes in zebrafish 使用GBR 12909抑制多巴胺转运体，作为一种新型药理学工具来评估斑马鱼双相情感障碍样神经行为表型。

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2024-10-21 DOI: 10.1016/j.bbr.2024.115302

Dopamine (DA) is a neurotransmitter that plays an important role in brain physiology. Changes in DA-mediated signaling have been implicated with the pathophysiology of various neuropsychiatric conditions. Bipolar disorder (BD) is a mental disorder, characterized by alterning between manic/hypomanic and depressive mood. In experimental research, the pharmacological inhibition of DA reuptake using GBR 12909 serves as a tool to elicit BD-like phenotypes. Alternative model organisms, such as the zebrafish (Danio rerio), have been considered important systems for investigating the neurobehavioral changes involved in different neuropsychiatric conditions, including BD. Here, we discuss the use of GBR 12909 as a novel pharmacological strategy to mimic BD-like phenotypes in zebrafish models. We also emphasize the well-conserved DA-mediated signaling in zebrafish and the early expression of dopaminergic biomarkers in the brain, especially focusing on dopamine transporter (DAT), the main target of GBR 12909. Finally, we discuss potential advantages and limitations in the field, the perspectives of using GBR 12909 in BD research, and how distinct validation criteria (i.e., face, predictive, and construct validity) can be assessed in translational approaches using zebrafish-based models.

多巴胺（DA）是一种神经递质，在大脑生理中发挥着重要作用。多巴胺介导的信号变化与多种神经精神疾病的病理生理学有关。双相情感障碍（BD）是一种精神疾病，其特征是躁狂/躁狂和抑郁情绪交替出现。在实验研究中，使用 GBR 12909 对 DA 再摄取进行药理抑制是诱发双相情感障碍样表型的一种工具。斑马鱼（Danio rerio）等替代模式生物被认为是研究包括 BD 在内的不同神经精神疾病所涉及的神经行为变化的重要系统。在此，我们将讨论使用 GBR 12909 作为一种新型药理学策略，在斑马鱼模型中模拟 BD 类表型。我们还强调了斑马鱼体内保存完好的由 DA 介导的信号传导，以及多巴胺能生物标记物在大脑中的早期表达，尤其是多巴胺转运体（DAT），它是 GBR 12909 的主要靶点。最后，我们讨论了该领域的潜在优势和局限性、在BD研究中使用GBR 12909的前景，以及在使用基于斑马鱼的模型的转化方法中如何评估不同的验证标准（即表面效度、预测效度和构建效度）。

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引用次数: 0

Between Scylla and Charybdis: Fixed-ratio avoidance response effort and unavoidable shock extinction in humans 在 Scylla 和 Charybdis 之间：人类的固定比率回避反应努力和不可避免的冲击消退。

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2024-10-20 DOI: 10.1016/j.bbr.2024.115299

Avoidance of potential threat may become maladaptive when it is indiscriminate and resistant to change. Here, we investigated the resistance to change of high and low avoidance response effort when avoidance extinction involved unavoidable presentations of the aversive event (shock) in humans. Following fear conditioning, participants prevented upcoming shock delivery by responding on high (i.e., fixed ratio, FR-20) and low (FR-5) negative reinforcement schedules. Next, noneliminable shock was used for an avoidance extinction procedure whereby responding was followed by, rather than prevented, shock. During a subsequent standard extinction and response prevention test phase, we found that High effort (FR-20) avoidance would be more readily extinguished than Low effort (FR-5) avoidance. It was also predicted that fear, threat expectancy, and psychophysiological (skin conductance) responses would decrease on avoidable trials and increase on unavoidable trials before extinguishing to low levels. It was found that in the final extinction re-test phase when avoidance was possible, responding increased, particularly for low effort cues. Both fear and expectancy remained high. Individual differences on clinically relevant measures of trait anxiety, intolerance of uncertainty and experiential avoidance were associated with greater levels of fear and threat expectancy. Overall, unavoidable shock extinction may hold promise for further translational investigations of avoidance learning, extinction, and clinical treatment development.

如果对潜在威胁的回避不加区分且抗拒改变，那么这种回避可能会变得不适应。在这里，我们研究了当人类的回避灭绝涉及到不可避免地出现厌恶事件（电击）时，高回避反应努力和低回避反应努力的变化阻力。在恐惧条件反射之后，参与者通过在高负性强化计划（即固定比率，FR-20）和低负性强化计划（FR-5）上做出反应来防止即将到来的电击。接下来，不可消除的电击被用于回避消减程序，在该程序中，反应后会出现电击，而不是阻止电击。在随后的标准消退和反应预防测试阶段，我们发现高努力（FR-20）回避比低努力（FR-5）回避更容易消退。我们还预测，恐惧、威胁预期和心理生理（皮肤传导）反应在可避免的试验中会降低，而在不可避免的试验中会升高，然后熄灭到低水平。研究发现，在最后的消亡再测试阶段，当有可能回避时，反应会增加，尤其是对低强度线索的反应。恐惧和期望值仍然很高。与临床相关的特质焦虑、不确定性不耐受性和经验回避的个体差异与更高水平的恐惧和威胁预期有关。总之，不可避免的冲击消退可能会为回避学习、消退和临床治疗开发的进一步转化研究带来希望。

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引用次数: 0

Involvement of the serotonergic, GABAergic and glutamatergic systems of the rostral anterior cingulate cortex in the trait and state anxiety of adult male Wistar rats. 喙状前扣带回皮层的血清素能、GABA 能和谷氨酸能系统参与成年雄性 Wistar 大鼠的性状和状态焦虑。

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2024-10-19 DOI: 10.1016/j.bbr.2024.115298

Despite significant advancements to understand of the neural circuitry involved in anxiety, the neurobiology of trait anxiety remains unclear. The rostral anterior cingulate cortex (rACC) and various pathways have been implicated in its regulation, making it a key to trait anxiety. The present study aimed to investigate the role of these neurotransmitter systems in the rACC in trait anxiety. Since trait anxiety is known to modulate state anxiety, we further investigated this relationship. Specifically, in Experiment I, we used animals with high trait anxiety; in Experiment II, we used animals with low trait anxiety; and in Experiment III, we used animals with medium trait anxiety. Before each behavioral assessment, drugs that either increased or decreased serotonergic (Fluoxetine or WAY-100635), GABAergic (Muscimol or Bicuculline), and glutamatergic (NMDA or Ketamine) neurotransmission in the rACC were administered, along with their respective controls. Additionally, in Experiment IV, all animals from the previous experiments were subjected to the Elevated Plus Maze (EPM) and Hole board (HB) test and evaluated without taking into account their trait anxiety levels. The results of the present study showed that, in Exp I, the modulation of the serotonergic, GABAergic and glutamatergic systems in the rACC decreased trait anxiety in highly anxious rats, while by submitting the animals to HB, the administration of fluoxetine increased state anxiety. In Exp II, the modulation of all systems increased trait anxiety in rats with low trait anxiety, whereas, in HB, state anxiety levels were increased with the administration of NMDA. In Exp III, only the modulation of the glutamatergic system, with NMDA, increased both trait and state anxiety levels. However, none of the evaluated neurotransmitter systems altered the state anxiety modeled in the EPM. Overall, the results of the present study provide new insights into the role of the neurotransmitter systems in the rACC in the regulation of trait anxiety and state anxiety.

尽管在了解焦虑所涉及的神经回路方面取得了重大进展，但特质焦虑的神经生物学仍不清楚。喙状前扣带回皮层（rACC）和各种通路都与它的调节有关，因此它是特质焦虑的关键。本研究旨在探讨这些神经递质系统在性焦虑中的作用。众所周知，特质焦虑会调节状态焦虑，因此我们进一步研究了这种关系。具体来说，在实验一中，我们使用了高特质焦虑的动物；在实验二中，我们使用了低特质焦虑的动物；在实验三中，我们使用了中等特质焦虑的动物。在每次行为评估之前，我们都会在 rACC 中使用增加或减少血清素能（氟西汀或 WAY-100635）、GABA 能（Muscimol 或 Bicuculline）和谷氨酸能（NMDA 或 Ketamine）神经递质的药物，并同时使用相应的对照药物。此外，在实验四中，对之前实验中的所有动物进行了高架迷宫（EPM）和孔板（HB）测试，并在不考虑其特质焦虑水平的情况下进行了评估。本研究的结果表明，在实验一中，调节 rACC 中的血清素能、GABA 能和谷氨酸能系统可降低高度焦虑大鼠的特质焦虑，而让动物接受 HB 测试则可增加其状态焦虑。在实验 II 中，对所有系统的调节都会增加低特质焦虑大鼠的特质焦虑，而在 HB 中，服用 NMDA 会增加状态焦虑水平。在实验三中，只有使用 NMDA 对谷氨酸能系统进行调节，才能同时提高特质焦虑和状态焦虑水平。然而，所评估的神经递质系统均未改变 EPM 中的状态焦虑模型。总之，本研究的结果为了解 rACC 中的神经递质系统在调节特质焦虑和状态焦虑中的作用提供了新的视角。

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引用次数: 0

Towards imagined speech: Identification of brain states from EEG signals for BCI-based communication systems 迈向想象中的语音：从脑电图信号中识别大脑状态，用于基于 BCI 的通信系统。

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2024-10-18 DOI: 10.1016/j.bbr.2024.115295

Background

The electroencephalogram (EEG) based brain-computer interface (BCI) system employing imagined speech serves as a mechanism for decoding EEG signals to facilitate control over external devices or communication with the external world at the moment the user desires. To effectively deploy such BCIs, it is imperative to accurately discern various brain states from continuous EEG signals when users initiate word imagination.

New method

This study involved the acquisition of EEG signals from 15 subjects engaged in four states: resting, listening, imagined speech, and actual speech, each involving a predefined set of 10 words. The EEG signals underwent preprocessing, segmentation, spatio-temporal and spectral analysis of each state, and functional connectivity analysis using the phase locking value (PLV) method. Subsequently, five features were extracted from the frequency and time-frequency domains. Classification tasks were performed using four machine learning algorithms in both pair-wise and multiclass scenarios, considering subject-dependent and subject-independent data.

Results

In the subject-dependent scenario, the random forest (RF) classifier achieved a maximum accuracy of 94.60 % for pairwise classification, while the artificial neural network (ANN) classifier achieved a maximum accuracy of 66.92 % for multiclass classification. In the subject-independent scenario, the random forest (RF) classifier achieved maximum accuracies of 81.02 % for pairwise classification and 55.58 % for multiclass classification. Moreover, EEG signals were classified based on frequency bands and brain lobes, revealing that the theta (θ) and delta (δ) bands, as well as the frontal and temporal lobes, are sufficient for distinguishing between brain states.

Conclusion

The findings promise to develop a system capable of automatically segmenting imagined speech segments from continuous EEG signals.

背景：基于脑电图（EEG）的脑机接口（BCI）系统采用想象语音作为解码脑电信号的机制，以便在用户希望的时刻控制外部设备或与外部世界交流。为了有效地部署此类 BCI，必须从连续脑电信号中准确分辨出用户发起词语想象时的各种大脑状态：本研究采集了 15 名受试者在四种状态下的脑电信号：静止、聆听、想象言语和实际言语，每种状态都涉及一组预定义的 10 个单词。脑电信号经过预处理、分割、每种状态的时空和频谱分析，以及使用锁相值（PLV）方法进行功能连接分析。随后，从频域和时频域提取了五个特征。使用四种机器学习算法在成对和多类情景下执行分类任务，同时考虑与受试者相关和与受试者无关的数据：在与主体相关的场景中，随机森林（RF）分类器的成对分类准确率最高达 94.60%，而人工神经网络（ANN）分类器的多分类准确率最高达 66.92%。在与受试者无关的情况下，随机森林（RF）分类器的成对分类准确率最高为 81.02%，多分类准确率最高为 55.58%。此外，还根据频带和脑叶对脑电图信号进行了分类，发现θ和δ频带以及额叶和颞叶足以区分大脑状态：这些研究结果有望开发出一种能够从连续脑电信号中自动分割想象语音片段的系统。

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引用次数: 0

An unescapable looming threat paradigm for assessing anxiety-like responses in rats 用于评估大鼠焦虑样反应的无法逃避的迫在眉睫的威胁范例。

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2024-10-18 DOI: 10.1016/j.bbr.2024.115296

Rapidly approaching visual stimuli (i.e. looming objects) are known to evoke unconditioned defense responses across species. In rodents, this threat reactivity repertoire includes freezing and fleeing behavior. Although components of the circuitry underlying unconditioned response to a looming threat have been elucidated, both a temporal characterization and drug effects on the freezing response have not yet been reported. Here, we describe a modified version of a looming threat task in which no escape route is available. In this task, we observed unconditioned freezing prior to, during, and after exposure to a looming threat stimulus. In Long Evans (LE) and Sprague-Dawley (SD) rats, we report looming stimulus-specific freezing response. We further explored the specificity and pharmacosensitivity of this response in male and female LE rats. Administration of a GABA-A receptor negative allosteric modulator (FG-7142) did not re-establish freezing in habituated animals; however, administration of a GABA-A receptor positive allosteric modulator (diazepam) in naïve LEs significantly reduced freezing during the post-looming period in a sex-dependent manner. Presentation of an unescapable looming stimulus results in freezing that extends beyond the acute threat exposure. Because freezing responses outlast the initial threat, and display only modest sensitivity to conventional anxiolytic therapy, this may represent a platform for screening agents in treatment-refractory anxiety.

众所周知，快速逼近的视觉刺激（如若隐若现的物体）会唤起不同物种的无条件防御反应。在啮齿类动物中，这种威胁反应包括冻结和逃离行为。虽然已经阐明了对迫近威胁的无条件反应的基础电路成分，但尚未报道冻结反应的时间特征和药物效应。在这里，我们描述了一个没有逃生路线的迫在眉睫威胁任务的改进版。在这项任务中，我们观察了暴露于迫在眉睫的威胁刺激之前、期间和之后的无条件冻结。在 Long Evans（LE）大鼠和 Sprague-Dawley （SD）大鼠身上，我们报告了隐约可见的刺激特异性冻结反应。我们进一步探索了这种反应在雄性和雌性 LE 大鼠中的特异性和药敏性。给予 GABA-A 受体负性异位调节剂（FG-7142）并不能重新建立习得动物的冻结反应；然而，在天真的 LEs 中给予 GABA-A 受体正性异位调节剂（地西泮）则能以性别依赖的方式显著减少徘徊后期间的冻结反应。无法逃避的迫近刺激会导致冷冻反应超过急性威胁暴露期。由于凝固反应持续时间超过了最初的威胁，而且对传统抗焦虑疗法的敏感性不高，因此这可能是筛选治疗难治性焦虑症药物的一个平台。

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引用次数: 0

HINT1 promotes neuronal apoptosis and triggers schizophrenia-like behavior in rats HINT1 促进神经元凋亡并引发大鼠精神分裂症样行为

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2024-10-18 DOI: 10.1016/j.bbr.2024.115297

This study aims to investigate the mechanism by which Histidine triad nucleotide-binding protein 1 (HINT1) promotes hippocampal neuronal apoptosis, triggering schizophrenia (SZ)-like behavior in rats. By establishing a rat SZ-like model, we assessed learning, memory, emotional response, and cognitive function through the Morris Water Maze, auditory startle response, and open field tests. HINT1 expression in the hippocampus was analyzed via RT-PCR and Western blot. We also created a HINT1 overexpression model in hippocampal neuronal cells to analyze its effects on cell proliferation and apoptosis. This analysis was conducted using the CCK-8 assay and flow cytometry, along with the quantification of apoptosis-related proteins and neurotrophic factors. Our findings indicated that the SZ-like model rats exhibited diminished learning and memory abilities, altered emotional reactions, and impaired cognitive functions, alongside a notable increase in HINT1 mRNA and protein levels. HINT1 overexpression was observed to inhibit hippocampal neuronal cell proliferation and promote apoptosis, with an increase in the expression of pro-apoptotic proteins and a decrease in neurotrophic factors. These results suggest HINT1's role in the onset and development of SZ-like behavior through its upregulation and induction of apoptosis in hippocampal neuronal cells, underlining its potential as a therapeutic target.

本研究旨在探讨组氨酸三核苷酸结合蛋白1（HINT1）促进海马神经元凋亡、引发大鼠精神分裂症（SZ）样行为的机制。通过建立大鼠类精神分裂症模型，我们通过莫里斯水迷宫、听觉惊吓反应和开阔地测试评估了大鼠的学习、记忆、情绪反应和认知功能。我们通过 RT-PCR 和 Western 印迹分析了海马中 HINT1 的表达。我们还在海马神经元细胞中创建了一个 HINT1 过表达模型，以分析其对细胞增殖和凋亡的影响。这项分析是通过 CCK-8 检测法和流式细胞术以及凋亡相关蛋白和神经营养因子的定量分析进行的。我们的研究结果表明，类 SZ 模型大鼠表现出学习和记忆能力减退、情绪反应改变和认知功能受损，同时 HINT1 mRNA 和蛋白水平显著升高。研究观察到，HINT1 的过表达抑制了海马神经元细胞的增殖，促进了细胞凋亡，同时促凋亡蛋白的表达增加，神经营养因子的表达减少。这些结果表明，HINT1通过上调和诱导海马神经元细胞凋亡，在SZ样行为的发生和发展过程中发挥作用，并强调了其作为治疗靶点的潜力。

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引用次数: 0

Effect of chronic alcohol exposure and single-prolonged stress on conditioned fear behavior 慢性酒精暴露和单次长期应激对条件性恐惧行为的影响

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2024-10-16 DOI: 10.1016/j.bbr.2024.115294

The present study investigated the impact of chronic intermittent ethanol (CIE) exposure and single-prolonged stress (SPS) on the acquisition of fear memories in both male and female Wistar rats. Adult rats were first subjected to CIE by vapor inhalation followed by SPS. Following a subsequent 8-day incubation period, the rats underwent a Pavlovian fear conditioning procedure (tone-shock pairings) followed by cued-tone extinction training, and then testing of extinction recall memory and fear renewal memory. In control animals that had not been exposed to either CIE or SPS, female rats exhibited significantly lower levels of freezing compared to male rats during tone-shock pairings. This lower level of freezing in female rats during conditioning was associated with an increased speed of movement compared to males. Also compared to males, female rats exhibited lower levels of fear extinction, recall, and renewal. Exposure to CIE, SPS, or CIE+SPS had no effect on freezing during the cued-conditioning, extinction, or extinction recall phases of the testing procedure in either sex. In fear renewal, CIE exposure decreased freezing in male but not female rats, while SPS increased freezing in female but not male rats. CIE exposure significantly reduced freezing during the fear renewal phase. Taken together, these results provide further evidence that male and female rats adopt different avoidance strategies for threat responding. These results also revealed that prior exposure to CIE, SPS, or CIE+SPS had minimal effects on threat responding using conditioned freezing as an indicator of fear responsivity.

本研究调查了慢性间歇性乙醇暴露（CIE）和单次持续应激（SPS）对雄性和雌性Wistar大鼠获得恐惧记忆的影响。成年大鼠首先通过吸入蒸汽接受 CIE，然后接受 SPS。经过 8 天的潜伏期后，大鼠接受巴甫洛夫恐惧条件反射训练（音调-冲击配对），然后进行提示音消退训练，最后测试消退记忆和恐惧更新记忆。在没有接触过 CIE 或 SPS 的对照组动物中，雌性大鼠在音调冲击配对过程中表现出的冻结水平明显低于雄性大鼠。与雄性大鼠相比，雌性大鼠在条件反射过程中较低的冻结水平与运动速度增加有关。此外，与雄性大鼠相比，雌性大鼠的恐惧消退、回忆和更新水平较低。在测试程序的诱导条件反射、消退或消退回忆阶段，暴露于CIE、SPS或CIE+SPS对雌雄大鼠的冻结都没有影响。在恐惧恢复过程中，暴露于CIE会减少雄性大鼠的冻结，但不会减少雌性大鼠的冻结；而暴露于SPS会增加雌性大鼠的冻结，但不会增加雄性大鼠的冻结。在恐惧更新阶段，暴露于CIE可明显减少冻结。综上所述，这些结果进一步证明了雄性和雌性大鼠在做出威胁反应时会采取不同的回避策略。这些结果还表明，使用条件冻结作为恐惧反应性的指标，事先暴露于 CIE、SPS 或 CIE+SPS 对威胁反应的影响微乎其微。

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引用次数: 0

DNA methylation profiles of transgenerational rat hyperactivity primed by silver nanoparticles: Comparison with valproate model rats of autism 纳米银颗粒引发的跨代大鼠多动症的 DNA 甲基化图谱：与丙戊酸钠自闭症模型大鼠的比较。

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research

Pub Date : 2024-10-16 DOI: 10.1016/j.bbr.2024.115293

There is an increasing body of evidence suggesting that a single exposure to certain chemicals can have transgenerational effects, with the underlying mechanism believed to be epigenetic. However, it remains largely unknown whether psychiatric conditions like ADHD or autism, induced by environmental chemicals, can be inherited across generations. Pregnant rats were purchased from a commercial breeder. On the 7th day of gestation (E7), they were divided into two groups: one group was orally exposed to silver nanoparticles (AgNP; 4 mg/kg), while the control group received vehicle alone. The subsequent generation (F1) underwent spontaneous motor activity (SMA) measurements at 8–11 weeks of age. For breeding at 26 weeks of age, rats with higher SMA were selected from hyperactive litters, while untreated rats were randomly selected. This process was continued for four generations in both groups. The AgNP-primed rats at 4th generation displayed significantly higher SMA, 1.8 times greater than that of untreated rats. Intraperitoneal injection of valproic acid (150 mg/kg), an epigenetic modifier to 5-day-old rats causes adult hyperactivity (1.4-fold), suggesting that epigenetic modification contributes to rat hyperactivity. Global DNA methylation profiles in the mesencephalon were positively correlated in both groups of hyperactive rats. Furthermore, there were 7–8 common genes showing both hypermethylation and hypomethylation, which are involved in neuronal development, neuronal function, transcriptional activity, DNA binding activity, cell differentiation, ubiquitination processes, or histone modification, including Pax 6 and Mecp 2. Thus, it is most likely that rats retain hyperactivity through mesencephalic DNA methylation status across transgeneration.

越来越多的证据表明，一次接触某些化学物质可能会产生跨代影响，其根本机制被认为是表观遗传。然而，由环境化学物质诱发的多动症或自闭症等精神疾病是否会跨代遗传，目前仍是一个未知数。妊娠大鼠购自商业饲养者。在妊娠第 7 天（E7），它们被分成两组：一组口服纳米银颗粒（AgNP；4 毫克/千克），而对照组只服用药物。下一代（F1）在 8~11 周龄时进行自发运动活动（SMA）测量。在 26 周龄时进行繁殖，从过度活跃的仔鼠中挑选 SMA 较高的大鼠，同时随机挑选未经处理的大鼠。这一过程在两组中都持续了四代。在第四代中，以 AgNP 为前体的大鼠的 SMA 明显较高，是未处理大鼠的 1.8 倍。向 5 日龄大鼠腹腔注射丙戊酸（150 毫克/千克）（一种表观遗传修饰剂）会导致成年大鼠过度活跃（1.4 倍），这表明表观遗传修饰是导致大鼠过度活跃的原因之一。两组多动大鼠间脑的DNA甲基化概况呈正相关。此外，有 7 至 8 个共同基因同时出现高甲基化和低甲基化，这些基因涉及神经元发育、神经元功能、转录活性、DNA 结合活性、细胞分化、泛素化过程或组蛋白修饰，包括 Pax 6 和 Mecp 2。因此，大鼠极有可能通过间脑 DNA 甲基化状态跨代保持过度活跃。

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引用次数: 0