大鼠成年前异常生活环境对其成年后恐惧记忆的影响(英文）

为了探讨早期饲养环境对成年后大鼠条件化恐惧的影响,实验采用巴氏恐惧条件化的方法对不同饲养环境下的大鼠进行了行为检测。具体操作为：把断奶后的大鼠饲养在3个不同的人工控制的环境中（丰富环境、社群环境和贫瘠环境）;8周后进行恐惧条件化训练和测试（指标为僵直百分比）,以及检测不同饲养环境下的大鼠的体重、自发活动和足部电击敏感性。结果显示：与社群组相比,丰富组的大鼠条件化僵直水平明显增加,而贫瘠组的明显减少;丰富和贫瘠环境明显的影响了大鼠的体重;不同环境对自发活动和足部电击敏感性没有影响。这些结果说明幼年期的丰富环境能提高成年后大鼠的由声音诱发的条件化恐惧反应,而贫瘠环境则削弱了这种反应。     

米非司酮对大鼠恐惧条件化及消退的影响

目的：研究米非司酮（RU486）对大鼠恐惧条件化及消退的影响。方法：大鼠连续4天给药（或生理盐水）后开始行为学实验,1 d适应环境;2 d进行恐惧条件化;3 d恐惧消退训练（也是条件化恐惧的表达检测阶段）;4 d进行消退记忆再现检测。结果：在恐惧表达阶段,两处理组与各自对照组大鼠的僵直水平组间差异都无显著性;在消退再现检测阶段,高剂量RU486组大鼠的僵直水平显著高于对照组,低剂量RU486组与对照组大鼠的僵直水平组间差异无显著性。结论：米非司酮损害消退记忆的再现,且这种损害与剂量有关。     

快速眼动睡眠剥夺对大鼠恐惧消退再现的影响

目的：研究两种实验范式AAA和ABA（A、B表示不同场景）中快速眼动睡眠剥夺（RSD）对大鼠恐惧消退再现的影响。方法：1d大鼠适应环境;2d进行恐惧条件化;3d恐惧消退训练并进行RSD;4d进行恐惧消退再现检测。结果：AAA实验范式中,在恐惧消退再现检测阶段,0～6hRSD组大鼠的僵直水平显著高于对照组（P〈0．05）,其他阶段处理组与对照组大鼠的僵直水平都无显著性;ABA实验范式中,各阶段处理组与对照组大鼠的僵直水平都无显著性。结论：不同实验范式中RSD对恐惧消退影响不同,并且这种影响依赖于睡眠剥夺的时段。     

快速眼动睡眠剥夺对大鼠线索性恐惧消退再现的影响

目的：研究RSD对大鼠线索性恐惧消退再现的影响。方法：1d大鼠适应环境;2d进行恐惧条件化;3d恐惧消退训练并进行RSD;4d进行恐惧消退再现检测。结果：在恐惧条件化及消退训练阶段,0-6hRSD组、6—12hRSD组与各自对照组大鼠的僵直水平组间差异都无显著性;在恐惧消退再现检测阶段,0-6hRSD组大鼠的僵直水平显著高于对照组,6-12hRSD组与对照组大鼠的僵直水平组间差异无显著性。结论：RSD损害消退记忆的再现,并且依赖于睡眠剥夺的时段。     

Wistar大鼠幼年期丰富环境刺激对其社会竞争行为的影响

目的：探讨大鼠幼年期丰富环境经历对其成年后焦虑样行为和社会竞争行为的影响。方法：幼年期Wistar大鼠（生后21天）分为标准饲养组（对照组）和丰富环境刺激（EE）组。对照组为持续在标准实验室饲养条件下饲养;丰富环境组为生后21天至行为学检查时持续在丰富环境下饲养。在生后70天进行行为学检测：采用高架十字迷宫方法测试焦虑样行为;采用社会优势管道试验观察社会竞争性行为。结果：高架十字迷宫实验结果显示,与对照组相比,丰富环境组在开放臂的时间和次数显著增加;优势管道实验结果显示丰富环境刺激组大鼠的社会竞争力明显下降。结论：大鼠幼年期丰富环境刺激可改善大鼠的焦虑样情绪,但导致大鼠社会竞争力下降。     

阿莫西林干预IHFA小鼠及对其成年后肠道菌群的影响

目的利用婴儿菌群人源化小鼠(IHFA小鼠)观察阿莫西林对其干预后及成年后肠道菌群的影响。方法新生Balb/c无菌小鼠接种纯母乳喂养的婴儿粪便获得IHFA小鼠。7~21日龄灌胃给予100mg/kg阿莫西林,对照组给予等量的生理盐水。采用变性梯度凝胶电泳(DGGE)检测小鼠在21日龄及53日龄的肠道菌群。结果 21日龄的阿莫西林处理组IHFA小鼠肠道菌群与正常对照组比较差异有统计学意义(P<0.05);即使在停药后饲养至53日龄的成年小鼠,阿莫西林处理组小鼠肠道菌群仍然存在细微差异。结论哺乳期治疗剂量阿莫西林处理不仅严重干扰小鼠肠道菌群结构,同时导致其成年后肠道菌群不能完全恢复。     

慢性不可预见性应激对大鼠恐惧条件反射和躯体感觉诱发电位的影响

目的:探讨慢性不可预见性应激对大鼠恐惧条件反射以及体感诱发电位的影响并分析可能的神经电生理机制。方法:26只雄性SD大鼠(190~200 g)随机分成两组(n=13):对照组和模型组。用慢性不可预见性应激刺激模型组大鼠,用恐惧条件反射实验检测两组大鼠的恐惧反应,用躯体感觉诱发电位检测大鼠脑电活动。结果:与对照组相比,模型组大鼠在恐惧记忆阶段不动时间百分比减小(56.64%±13.78%vs69.72%±18.10%,P<0.05),躯体感觉诱发电位的第二个正向波(P2)潜伏期也明显缩短(70.54±10.13 msvs78.46±7.80 ms,P<0.05)。相关性分析显示大鼠恐惧条件反射的不动时间与躯体感觉诱发电位潜伏期存在正相关(r=0.507,P<0.05)。结论:慢性不可预见性应激抑制大鼠恐惧反应,并缩短体表感觉诱发电位的潜伏期,恐惧反应行为与体感诱发电位潜伏期存在正相关,提示大鼠恐惧反应与体表感觉诱发电位可能有共同的神经递质机制。     

急性恐惧应激对大鼠行为、激素水平及脑Erk1/2活化表达的影响

目的:探讨急性恐惧应激对大鼠情感行为、激素水平及不同脑区Erk1/2活化表达的影响。方法:采用足电击 白噪声刺激方式建立急性恐惧应激大鼠模型,观察其情感行为的改变;放射免疫法及荧光分光光度法检测血浆和脑组织激素水平;Westernblot检测Erk1/2的活化表达。结果:应激后大鼠旷场活动性降低、拒俘反应性增加、惊吓反应增强(P<0.01);血浆及脑组织去甲肾上腺素、5-羟色胺、皮质醇水平增高,而肾上腺髓质素水平降低(P<0.01);海马、纹状体、前额皮质、小脑等脑区磷酸化Erk1/2蛋白的表达均显著增高(P<0.01)。结论:急性恐惧应激可以显著影响大鼠的情感行为和激素水平,Erk1/2蛋白磷酸化水平的增高可能参与了急性恐惧应激所致的情感行为异常。     

新生期触觉刺激和母婴分离对雌性大鼠成年后的焦虑和情绪记忆的影响

采用split-litter法对仔鼠进行分组和处理,共5组NTS组(未经实验人员抓握和标记),PND2—9TS组和PND10—17TS组(分别在仔鼠出生后的2—9天、10—17天,每天短暂抓握和标记仔鼠),PND2—9MS组和PND10—17MS组(分别在仔鼠出生后的2—9天、10—17天,除了按TS组相同方式抓握并在不同部位标记外,每天把仔鼠与母鼠分离1h)。待雌鼠成年后,进行明/暗箱测试和一次性被动回避反应测试。结果发现与NTS组相比,PND2—9TS组和PND10—17TS组的雌鼠在明/暗箱测试中停留于明室的累计时间明显较长,在被动回避作业中的重测试潜伏期也明显较长,表明新生期的触觉刺激经历减少雌性大鼠成年后在新异环境中的焦虑,并改善情绪记忆。与相应TS组相比,MS处理组的所有行为指标都无显著性差异,说明短时间母婴分离对雌鼠成年后的焦虑和情绪记忆无明显影响。结果提示,新生期的触觉刺激和母婴分离经历对仔鼠神经系统的发育产生不同的长期效应。     

淋巴瘤幸存者复发恐惧的影响因素及认知行为干预对患者生活质量和心理状态的影响

摘要 目的：分析淋巴瘤幸存者复发恐惧（FCR）的影响因素,并分析认知行为干预对患者生活质量和心理状态的影响。方法：本次研究为回顾性调查研究,选取2018年7月~2021年6月期间我院收治的淋巴瘤患者80例,根据病历资料获取患者婚姻状况、疾病分期、工作状况、年龄、治愈时间、文化程度、疾病类型、性别、医疗费用承担情况、家庭人均月收入。采用多因素Logistic回归分析淋巴瘤幸存者FCR的影响因素。将80例淋巴瘤患者分为对照组和干预组,各为40例。对照组给予常规处理,干预组在此基础上接受认知行为干预,对比两组生活质量和心理状态变化。结果：淋巴瘤幸存者FCR总分为（86.90±5.96）分。不同婚姻状况、年龄、疾病分期、家庭人均月收入的患者FCR总分对比差异有统计学意义（P<0.05）。多因素Logistic回归分析显示家庭人均月收入、婚姻状况、疾病分期、年龄是淋巴瘤幸存者FCR的影响因素（P<0.05）。干预后,两组生理职能、躯体疼痛、精神健康、生理功能、总体健康、情感职能、活力、社会功能维度评分均较干预前升高,且干预组高于对照组（P<0.05）。干预组干预后的恐惧疾病进展简化量表（FoP-Q-SF）评分低于对照组（P<0.05）。结论：淋巴瘤幸存者的FCR应得到重视,尤其针对年龄偏低、婚姻状况为离异/未婚/丧偶、家庭人均月收入偏低、疾病分期高的人群,给予认知行为干预后,可提高患者的生活质量和心理状态。     

Effects of Methamphetamine Exposure on Fear Learning and Memory in Adult and Adolescent Rats

Methamphetamine (meth) use is often comorbid with anxiety disorders, with both conditions predominant during adolescence. Conditioned fear extinction is the most widely used model to study the fear learning and regulation that are relevant for anxiety disorders. The present study investigates how meth binge injections or meth self-administration affect subsequent fear conditioning, extinction and retrieval in adult and adolescent rats. In experiment 1, postnatal day 35 (P35—adolescent) and P70 (adult) rats were intraperitoneally injected with increasing doses of meth across 9 days. At P50 or P85, they underwent fear conditioning followed by extinction and test. In experiments 2a–c, P35 or P70 rats self-administered meth for 11 days then received fear conditioning at P50 or P85, followed by extinction and test. We observed that meth binge exposure caused a significant disruption of extinction retrieval in adult but not adolescent rats. Interestingly, meth self-administration in adolescence or adulthood disrupted acquisition of conditioned freezing in adulthood. Meth self-administration in adolescence did not affect conditioned freezing in adolescence. These results suggest that intraperitoneal injections of high doses of meth and meth self-administration have dissociated effects on fear conditioning and extinction during adulthood, while adolescent fear conditioning and extinction are unaffected.

     

Impaired Extinction of Learned Contextual Fear Memory in Early Growth Response 1 Knockout Mice

Inductive expression of early growth response 1 (Egr-1) in neurons is associated with many forms of neuronal activity. However, only a few Egr-1 target genes are known in the brain. The results of this study demonstrate that Egr-1 knockout (KO) mice display impaired contextual extinction learning and normal fear acquisition relative to wild-type (WT) control animals. Genome-wide microarray experiments revealed 368 differentially expressed genes in the hippocampus of Egr-1 WT exposed to different phases of a fear conditioning paradigm compared to gene expression profiles in the hippocampus of KO mice. Some of genes, such as serotonin receptor 2C (Htr2c), neuropeptide B (Npb), neuronal PAS domain protein 4 (Npas4), NPY receptor Y1 (Npy1r), fatty acid binding protein 7 (Fabp7), and neuropeptide Y (Npy) are known to regulate processing of fearful memories, and promoter analyses demonstrated that several of these genes contained Egr-1 binding sites. This study provides a useful list of potential Egr-1 target genes which may be regulated during fear memory processing.     

Fear conditioning induces distinct patterns of gene expression in lateral amygdala

The lateral nucleus of the amygdala (LA) has been implicated in the formation of long-term associative memory (LTM) of stimuli associated with danger through fear conditioning. The current study aims to detect genes that are expressed in LA following associative fear conditioning. Using oligonucleotide microarrays, we monitored gene expression in rats subjected to paired training where a tone co-terminates with a footshock, or unpaired training where the tone and footshock are presented in a non-overlapping manner. The paired protocol consistently leads to auditory fear conditioning memory formation, whereas the unpaired protocol does not. When the paired group was compared with the unpaired group 5 h after training, the expression of genes coding for the limbic system-associated membrane protein (Lsamp), kinesin heavy chain member 2 (Kif2), N -ethylmaleimide-sensitive fusion protein (NSF) and Hippocalcin-like 4 protein (Hpcal4) was higher in the paired group. These genes encode proteins that regulate neuronal axonal morphology (Lsamp, Kif2), presynaptic vesicle cycling and release (Hpcal4 and NSF), and AMPA receptor maintenance in synapses (NSF). Quantitative real-time PCR (qPCR) showed that Kif2 and Lsamp are expressed hours following fear conditioning but minutes after unpaired training. Hpcal4 is induced by paired stimulation only 5 h after the training. These results show that fear conditioning induces a unique temporal activation of molecular pathways involved in regulating synaptic transmission and axonal morphology in LA, which is different from non-associative stimulation.     

NMDA Receptors Mediate Consolidation of Contextual Memory in the Hippocampus after Context Preexposure

Male Wistar rats received bilateral infusions of vehicle (VEH) or aminophosphonopentanoic acid (AP5), an N-metil-D-aspartate (NMDA) receptor antagonist, into the dorsal hippocampus immediately after inhibitory avoidance (IA) training. Intrahippocampal infusion of AP5 blocked 24 h IA retention. In the second experiment, animals were preexposed to the IA training context 24 h prior to training and received an infusion of either VEH or AP5 immediately after the preexposure trial and a second infusion of VEH or AP5 immediately after IA training. AP5 did not affect retention in animals preexposed to the IA box and given VEH after preexposure, but blocked retention when given after both preexposure and training. AP5 impaired retention in rats preexposed to an environment distinct from the IA box. These results suggest that NMDA receptors in the dorsal hippocampus mediate the formation of a contextual representation of the task environment.     

Genetic Perturbation of TIA1 Reveals a Physiological Role in Fear Memory

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Effects of Long-Term Ayahuasca Administration on Memory and Anxiety in Rats

Ayahuasca is a hallucinogenic beverage that combines the action of the 5-HT_2A/2C agonist N,N-dimethyltryptamine (DMT) from Psychotria viridis with the monoamine oxidase inhibitors (MAOIs) induced by beta-carbonyls from Banisteriopsis caapi. Previous investigations have highlighted the involvement of ayahuasca with the activation of brain regions known to be involved with episodic memory, contextual associations and emotional processing after ayahuasca ingestion. Moreover long term users show better performance in neuropsychological tests when tested in off-drug condition. This study evaluated the effects of long-term administration of ayahuasca on Morris water maze (MWM), fear conditioning and elevated plus maze (EPM) performance in rats. Behavior tests started 48h after the end of treatment. Freeze-dried ayahuasca doses of 120, 240 and 480 mg/kg were used, with water as the control. Long-term administration consisted of a daily oral dose for 30 days by gavage. The behavioral data indicated that long-term ayahuasca administration did not affect the performance of animals in MWM and EPM tasks. However the dose of 120 mg/kg increased the contextual conditioned fear response for both background and foreground fear conditioning. The tone conditioned response was not affected after long-term administration. In addition, the increase in the contextual fear response was maintained during the repeated sessions several weeks after training. Taken together, these data showed that long-term ayahuasca administration in rats can interfere with the contextual association of emotional events, which is in agreement with the fact that the beverage activates brain areas related to these processes.     

The Influence of Social Isolation and Enriched Environment on Fear Conditioning in Rats after Early Proinflammatory Stress

Journal of Evolutionary Biochemistry and Physiology - The effect of social isolation or enriched environment on fear conditioning and extinction was studied in 3.5–4-month-old rats exposed to...