448 resultados para Maze


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Numerous observations in clinical and preclinical studies indicate that the developing brain is particular sensitive to lead (Pb)'s pernicious effects. However, the effect of gestation-only Pb exposure on cognitive functions at maturation has not been studied. We investigated the potential effects of three levels of Pb exposure (low, middle, and high Pb: 0.03%, 0.09%, and 0.27% of lead acetate-containing diets) at the gestational period on the spatial memory of young adult offspring by Morris water maze spatial learning and fixed location/visible platform tasks. Our results revealed that three levels of Pb exposure significantly impaired memory retrieval in male offspring, but only female offspring at low levels of Pb exposure showed impairment of memory retrieval. These impairments were not due to the gross disturbances in motor performance and in vision because these animals performed the fixed location/visible platform task as well as controls, indicating that the specific aspects of spatial learning/memory were impaired. These results suggest that exposure to Pb during the gestational period is sufficient to cause long-term learning/memory deficits in young adult offspring. (C) 2003 Elsevier Inc. All rights reserved.

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The hippocampus, being sensitive to stress and glucocorticoids, plays significant roles in certain types of learning and memory. Therefore, the hippocampus is probably involved in the increasing drug use, drug seeking, and relapse caused by stress. We have studied the effect of stress with morphine on synaptic plasticity in the CA1 region of the hippocampus in vivo and on a delayed-escape paradigm of the Morris water maze. Our results reveal that acute stress enables long-term depression (LTD) induction by low-frequency stimulation (LFS) but acute morphine causes synaptic potentiation. Remarkably, exposure to an acute stressor reverses the effect of morphine from synaptic potentiation ( similar to 20%) to synaptic depression ( similar to 40%), precluding further LTD induction by LFS. The synaptic depression caused by stress with morphine is blocked either by the glucocorticoid receptor antagonist RU38486 or by the NMDA-receptor antagonist D-APV. Chronic morphine attenuates the ability of acute morphine to cause synaptic potentiation, and stress to enable LTD induction, but not the ability of stress in tandem with morphine to cause synaptic depression. Furthermore, corticosterone with morphine during the initial phase of drug use promotes later delayed-escape behavior, as indicated by the morphine-reinforced longer latencies to escape, leading to persistent morphine-seeking after withdrawal. These results suggest that hippocampal synaptic plasticity may play a significant role in the effects of stress or glucocorticoids on opiate addiction.

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Previous Studies have demonstrated that in the pentylenetetrazol (PTZ) kindling model, recurrent seizures either impair or have no effect on learning and memory. However, the effects of brief seizures on learning and memory remain unknown. Here, we found

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Chronic exposure to opiates impairs hippocampal long-term potentiation (LTP) and spatial memory, but the underlying mechanisms remain to be elucidated. Given the well known effects of adenosine, an important neuromodulator, on hippocampal neuronal excitability and synaptic plasticity, we investigated the potential effect of changes in adenosine concentrations on chronic morphine treatment-induced impairment of hippocampal CA1 LTP and spatial memory. We found that chronic treatment in mice with either increasing doses (20-100 mg/kg) of morphine for 7 d or equal daily dose (20 mg/kg) of morphine for 12 d led to a significant increase of hippocampal extracellular adenosine concentrations. Importantly, we found that accumulated adenosine contributed to the inhibition of the hippocampal CA1 LTP and impairment of spatial memory retrieval measured in the Morris water maze. Adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine significantly reversed chronic morphine-induced impairment of hippocampal CA1 LTP and spatial memory. Likewise, adenosine deaminase, which converts adenosine into the inactive metabolite inosine, restored impaired hippocampal CA1 LTP. We further found that adenosine accumulation was attributable to the alteration of adenosine uptake but not adenosine metabolisms. Bidirectional nucleoside transporters (ENT2) appeared to play a key role in the reduction of adenosine uptake. Changes in PKC-alpha/beta activity were correlated with the attenuation of the ENT2 function in the short-term (2 h) but not in the long-term (7 d) period after the termination of morphine treatment. This study reveals a potential mechanism by which chronic exposure to morphine leads to impairment of both hippocampal LTP and spatial memory.

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1 It has not been uniform to date that the Ginkgo biloba extracts enhance cognitive function in aged animals, and the mechanisms of action remain difficult to elucidate. In this study, the Morris water maze task and electrophysiological methods were used

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Wistar rats, treated with the GABA(A) receptor agonist muscimol, were used to investigate the role of the hippocampal-prelimbic cortical (Hip-PLC) circuit in spatial learning in the Morris water maze task, and in passive avoidance learning in the step-thr

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Humans, like other animals, alter their behavior depending on whether a threat is close or distant. We investigated spatial imminence of threat by developing an active avoidance paradigm in which volunteers were pursued through a maze by a virtual predator endowed with an ability to chase, capture, and inflict pain. Using functional magnetic resonance imaging, we found that as the virtual predator grew closer, brain activity shifted from the ventromedial prefrontal cortex to the periaqueductal gray. This shift showed maximal expression when a high degree of pain was anticipated. Moreover, imminence-driven periaqueductal gray activity correlated with increased subjective degree of dread and decreased confidence of escape. Our findings cast light on the neural dynamics of threat anticipation and have implications for the neurobiology of human anxiety-related disorders.

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Most reinforcement learning models of animal conditioning operate under the convenient, though fictive, assumption that Pavlovian conditioning concerns prediction learning whereas instrumental conditioning concerns action learning. However, it is only through Pavlovian responses that Pavlovian prediction learning is evident, and these responses can act against the instrumental interests of the subjects. This can be seen in both experimental and natural circumstances. In this paper we study the consequences of importing this competition into a reinforcement learning context, and demonstrate the resulting effects in an omission schedule and a maze navigation task. The misbehavior created by Pavlovian values can be quite debilitating; we discuss how it may be disciplined.

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Animals repeat rewarded behaviors, but the physiological basis of reward-based learning has only been partially elucidated. On one hand, experimental evidence shows that the neuromodulator dopamine carries information about rewards and affects synaptic plasticity. On the other hand, the theory of reinforcement learning provides a framework for reward-based learning. Recent models of reward-modulated spike-timing-dependent plasticity have made first steps towards bridging the gap between the two approaches, but faced two problems. First, reinforcement learning is typically formulated in a discrete framework, ill-adapted to the description of natural situations. Second, biologically plausible models of reward-modulated spike-timing-dependent plasticity require precise calculation of the reward prediction error, yet it remains to be shown how this can be computed by neurons. Here we propose a solution to these problems by extending the continuous temporal difference (TD) learning of Doya (2000) to the case of spiking neurons in an actor-critic network operating in continuous time, and with continuous state and action representations. In our model, the critic learns to predict expected future rewards in real time. Its activity, together with actual rewards, conditions the delivery of a neuromodulatory TD signal to itself and to the actor, which is responsible for action choice. In simulations, we show that such an architecture can solve a Morris water-maze-like navigation task, in a number of trials consistent with reported animal performance. We also use our model to solve the acrobot and the cartpole problems, two complex motor control tasks. Our model provides a plausible way of computing reward prediction error in the brain. Moreover, the analytically derived learning rule is consistent with experimental evidence for dopamine-modulated spike-timing-dependent plasticity.

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一、大鼠海马-前额叶回路在学习记忆中的作用 解剖学研究证实大鼠和猴的海马结构(hippocampal formation, HF;本文‘海马 (hippocampus, Hip)’一词即指海马结构)和前额叶 (prefrontal cortex, PFC) 之间存在一条单向、同侧和单突触的神经回路,即海马-前额叶回路(Hip-PFC回路)。Hip和PFC均参与学习记忆等多种认知功能,PFC是工作记忆的关键脑区,而Hip是空间参考记忆的关键脑区。虽然人们已经对PFC和Hip进行了广泛深入的研究,但对Hip-PFC回路参与哪些认知功能还知之甚少。本研究的目的就是通过暂时阻断Hip-PFC回路,探讨其在学习和记忆中的作用。 在大鼠,Hip-PFC回路中的纤维主要从Hip腹部 (ventral hippocampus, VH)发出,投射到PFC的前边缘皮质(prelimbic cortex, PLC)、下边缘皮质 (infralimbic cortex, ILC) 和外侧前额叶 (lateral prefrontal cortex) 等亚区,其中PLC是Hip-PFC主要投射的区域。我们通过给动物安装慢性导管向脑内注射GABAA受体激动剂muscimol (MU) 阻断Hip-PFC回路。注射位点包括 ①双侧PLC,②双侧VH,③一侧VH和对侧PLC (VH-PLC)。我们首先观察了在PLC或VH局部注射MU对自由活动大鼠PLC和VH脑电功率的影响,并以此确定在行为实验中所用蝇蕈醇的剂量。然后采用T-迷宫空间交互延缓作业 (spatial delayed alternation task) 测试Hip-PFC回路被阻断的动物的空间工作记忆功能;采用被动回避作业 (passive avoidance task) 测试其情绪相关记忆的能力(训练前给药;24 h后重测试);采用Morris水迷宫作业 (Morris water maze task) 测试其空间参考记忆的能力(每天训练前给药;训练期(3 d)结束24 h后重测试)。结果表明:在大鼠PLC或VH局部注射0.5 μg/0.25μl MU后30 min显著抑制VH 和PLC的脑电功率 (VH, p < 0.01; PLC, p < 0.05 vs. PBS/baseline)。注射MU (0.5 μg/0.25μl) 到 ①双侧PLC、②双侧VH、③VH-PLC均显著降低动物在空间交互延缓作业 (All p < 0.001, vs. PBS) 和空间Morris水迷宫作业中的成绩 (All p < 0.05, vs. PBS),表明Hip-PFC回路在空间工作记忆(空间短时记忆)和在空间参考记忆(空间长时记忆)中均起重要作用。在空间交互延缓作业中,双侧PLC被抑制的大鼠的成绩显著低于双侧VH或VH-PLC被抑制的动物,说明PFC在空间工作记忆功能中占有主导地位。在被动回避作业中,双侧VH被抑制动物的回避反应的潜伏期显著短于对照动物 (p < 0.05 vs. PBS),说明双侧VH被抑制动物的情绪记忆受损;而双侧PLC或VH-PLC被抑制的动物其回避反应的潜伏期与对照动物无显著差异 (PLC, p > 0.9; VH-PLC, p > 0.3 vs. PBS),表明双侧PLC或VH-PLC被抑制的动物情绪记忆正常。被动回避作业的结果说明VH参与情绪记忆的形成,但Hip-PFC回路在情绪记忆形成中不起重要作用。 以上结果表明,大鼠Hip-PFC回路参与空间工作记忆和空间参考记忆而不是情绪记忆功能。情绪记忆的关键脑结构是杏仁复合体 (amygdala complex, AMC),VH与AMC有密切的纤维联系。VH被抑制的大鼠情绪记忆受损,说明情绪记忆可能与AMC-Hip回路有关。情绪记忆与空间记忆(参考记忆和工作记忆)在解剖上的分离说明,对于不同类型的记忆来说,其在脑内的信息加工过程是并行的。神经回路内部的信息加工过程则是串行的,回路上任何一个结构的破坏均可导致回路功能的损伤。本研究的结果为学习记忆的“多重记忆系统”理论和记忆信息加工的串行并行机制提供了新的实验证据。 二、芬克罗酮改善成年恒河猴空间工作记忆的谷氨酸机制 芬克罗酮是中科院昆明植物所郝小江等合成的取代吡咯烷酮类化合物。中科院昆明动物所蔡景霞等发现芬克罗酮能改善东莨菪碱、育亨宾等导致的多种动物的不同类型的学习记忆障碍,提高老年动物的学习记忆能力,尤其是老年猴的空间工作记忆。已证实芬克罗酮为部分钙激动剂,可使脑缺血沙土鼠脑内升高的谷氨酸降低,而使正常的沙土鼠海马胞外谷氨酸释放增加。那么芬克罗酮能否提高正常动物的学习记忆,其对正常动物学习记忆的提高是否与其增加谷氨酸的释放有关?本研究采用空间延缓反应作业和谷氨酸NMDA受体拮抗剂MK-801在正常成年猴恒河猴上探讨了以上问题。 结果表明,口服芬克罗酮可显著提高成年猴的空间工作记忆,其量效曲线呈倒‘U’形,符合许多促智药的量效特点。0.25 mg/kg和0.5 mg/kg为芬克罗酮的最佳有效剂量 (p < 0.05 vs. 安慰剂)。肌注MK-801 (0.1 mg/kg) 显著降低成年猴的空间工作记忆 (p < 0.01 vs. 安慰剂),而口服2.0 mg/kg和4.0 mg/kg的芬克罗酮则显著改善MK-801导致的工作记忆障碍 (p < 0.05 vs. MK-801)。芬克罗酮的所有测试剂量不影响猴在作业中的反应时 (p > 0.05 vs. 安慰剂),表明芬克罗酮在该剂量范围不影响动物的运动能力。 本研究结果提示,芬克罗酮可能通钙激动作用促进谷氨酸的释放,在一定剂量范围内提高胞外谷氨酸水平,提高正常动物的空间工作记忆等认知功能。 关键词:芬克罗酮,恒河猴,空间工作记忆,空间延缓反应作业,谷氨酸,MK-801

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BACKGROUND: Hypoxia and ischemia induce neuronal damage, decreased neuronal numbers and synaptophysin levels, and deficits in learning and memory functions. Previous studies have shown that lycium barbarum polysaccharide, the most effective component of barbary wolfberry fruit, has protective effects on neural cells in hypoxia-ischemia. OBJECTIVE: To investigate the effects of Naotan Pill on glutamate-treated neural cells and on cognitive function in juvenile rats following hypoxia-ischemia. DESIGN, TIME AND SETTING: The randomized, controlled, in vivo study was performed at the Cell Laboratory of Lanzhou University, Lanzhou Institute of Modern Physics of Chinese Academy of Sciences, and Department of Traditional Chinese Medicine of Gansu Provincial Rehabilitation Center Hospital, China from December 2005 to August 2006. The cellular neurobiology, in vitro experiment was conducted at the Institute of Human Anatomy, Histology, Embryology and Neuroscience, School of Basic Medical Sciences, Lanzhou University, and Department of Traditional Chinese Medicine of Gansu Provincial Rehabilitation Center Hospital, China from March 2007 to January 2008. MATERIALS: Naotan Pill, composed of barbary wolfberry fruit, danshen root, grassleaf sweetflag rhizome, and glossy privet fruit, was prepared by Gansu Provincial Rehabilitation Center, China. Rabbit anti-synaptophysin, choline acetyl transferase polyclonal antibody, streptavidin-biotin complex kit and diaminobenzidine kit (Boster, Wuhan, China), as well as glutamate (Hualian, Shanghai, China) were used in this study. METHODS: Cortical neural cells were isolated from neonatal Wistar rats. Neural cell damage models were induced using glutamate, and administered Naotan Pill prior to and following damage. A total of 54 juvenile Wistar rats were equally and randomly assigned into model, Naotan Pill, and sham operation groups. The left common carotid artery was ligated, and then rat models of hypoxic-ischemic injury were assigned to the model and Naotan Pill groups. At 2 days following model induction, rats in the Naotan Pill group were administered Naotan Pill suspension for 21 days. In the model and sham operation groups, rats received an equal volume of saline. MAIN OUTCOME MEASURES: Neural cell morphology was observed using an inverted phase contrast microscope. Survival rate of neural cells was measured by MTT assay. Synaptophysin and choline acetyl transferase expression was observed in the hippocampal CA1 region of juvenile rats using immunohistochemistry. Cognitive function was tested by the Morris water maze. RESULTS: Pathological changes were detected in glutamate-treated neural cells. Neural cell morphology remained normal after Naotan Pill intervention. Absorbance and survival rate of neural cells were significantly greater following Naotan Pill intervention, compared to glutamate-treated neural cells (P < 0.05). Synaptophysin and choline acetyl transferase expression was lowest in the hippocampal CA1 region in the model group and highest in the sham operation group. Significant differences among groups were observed (P < 0.05). Escape latency and swimming distance were significantly longer in the model group compared to the Naotan Pill group (P < 0.05). CONCLUSION: Naotan Pill exhibited protective and repair effects on glutamate-treated neural cells. Naotan Pill upregulated synaptophysin and choline acetyl transferase expression in the hippocampus and improved cognitive function in rats following hypoxia-ischemia.

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一、蜜蜂嗅觉学习记忆应用基础研究特殊气味的探测在刑侦工作中意义重大,常用的警犬探测和仪器分析都有其局限之处。蜜蜂嗅觉灵敏,且学习记忆能力突出,具有为刑侦工作所用的潜力。基于此,我们希望通过训练蜜蜂将其对糖水奖励的伸喙反应与指定气味建立条件反射的原理,配合适当的训练方法,达到利用蜜蜂探测危险气味的目的。在实验中,我们首先比较了不同喂养方式的蜜蜂在气味学习中的差别。由于低浓度气味无法直接使蜜蜂建立条件化,我们采用了逐渐降低气味浓度的方法,成功训练蜜蜂对低浓度(3.6×10-7) 醋酸气味建立了条件反射。结果如下: 1)自然放养与人工孵化两种不同喂养方式的蜜蜂,各两组,分别学习醋酸CS+/薄荷CS-,或柠檬CS+/薄荷CS-的气味配对。以“获得(CS+),巩固(CS-/CS+ CS+/CS- CS-/CS+),检测,干净空气假阳性检测”的顺序操作。结果显示自然放养蜜蜂对醋酸气味没有偏好(第一次给醋酸气味伸喙率:6%),学习醋酸气味能力较低(24小时后检测正确率:66%, n=25),相对应,该类蜜蜂对柠檬气味显示出明显偏好(第一次给柠檬气味伸喙率:41%,P< 0.01),而学习效果(检测正确率:50%,n=20)与醋酸组相近(P>0.05)。人工孵化的蜜蜂对醋酸气味学习能力较自然放养蜜蜂大大提高(检测正确率:96%, n=32, P<0.01),同时对柠檬的学习结果(检测正确率:80%, n=32)也明显提高(0.01

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1.老年猴视皮层神经元对图形对比度的反应及潜伏期特征: 在正常衰老过程中人类的视觉功能受到严重影响,例如空间和时间对比度敏感性下降以及信息处理时间的延长。虽然部分视觉功能的退化与眼睛的光学系统老化有关,但是它并不能解释所有视觉功能的下降。此外,我们以前的研究和别人的研究结果都表明衰老过程中视觉中枢系统功能的改变可能是视觉功能下降的主要原因。因此,利用单位放电记录技术(single-unit recording technique),我们比较了年轻猕猴和老年猕猴的初级视觉皮层(primary visual cortex,又称V1)神经元对比度反应之间的差异,以及V1和内侧颞叶(medial temporal cortex,MT)视觉区神经元反应潜伏期及其变异性之间的差异。结果显示,与年轻猴相比,老年猴V1区神经元对比度敏感性降低,同时伴随着神经元活动信噪比下降;老年猴V1区和MT区神经元反应潜伏期及其变异性显著增加。然而,两个年龄组MT区神经元平均潜伏期之间差异小于V1区神经元平均潜伏期之间的差异,说明MT区神经元能够自我调整老化带来的影响。另外,两个年龄组V1区神经元潜伏期和变异性都具有正相关关系,但是MT区神经元则没有这种相关性。这些结果表明,在老化过程中皮层神经元的对比度和潜伏期反应特性发生了改变。我们推测这种改变可能与视觉皮层内抑制系统功能的降低有关,但是具体的分子机制和神经环路还不清楚。总之,本实验的研究结果为更好的理解老年人在视觉信息处理中时间和空间对比度敏感性及处理速度下降提供了新线索。2.极低频磁场对脑功能的影响及眶额叶认知功能的研究: 实验目的:(1)研究极低频磁场(20 Hz, 14 mT)照射对长期吗啡处理引起的大鼠背侧海马神经元多巴胺D2密度降低的影响;(2)小鼠青春期长期极低频磁场(50 Hz, 2 mT)照射对空间学习记忆的影响;(3)初步探讨了眶额叶在大鼠新异性探索行为中的作用。实验1,我们用免疫组化的方法检测了大鼠背侧海马神经元多巴胺D2受体密度的变化。结果显示,在长期吗啡处理后戒断早期背侧海马神经元多巴胺D2受体密度相对于对照组减少,磁场和吗啡共同作用会强化这种适应,但是这种变化很快恢复正常。这些结果表明长期吗啡处理会引起海马多巴胺系统产生适应;磁场强化了长期吗啡处理对背侧海马多巴胺系统的影响,这为我们先前发现磁场照射延缓了大鼠条件位置偏好消退的研究结果提供了一个内在神经基础。实验2,我们分别用Y-迷宫(two-trial Y-maze)和Morris水迷宫两种行为装置研究了青春期早期磁场暴露对小鼠短时空间识别记忆和长时空间参考记忆的影响。结果显示,磁场暴露并没有影响小鼠Y-迷宫作业,但是提高了水迷宫任务的学习以及记忆保持。这些结果表明磁场对空间记忆的影响是任务依赖性的。实验3,我们用旷场和Y-迷宫两种行为装置研究了眶额叶电损伤对大鼠新异性探索行为的影响。结果显示,眶额叶受损并没有影响大鼠的神经运动能力,但是降低了大鼠在旷场中的行走距离和直立次数以及降低了在Y-迷宫新异臂中的探索时间和穿梭次数。这些结果表明,眶额叶的完整性对大鼠探索新异环境行为是必要的,这可能与眶额叶参与记忆或行为决策功能有关。

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The impact of astaxanthin-enriched algal powder on auxiliary memory improvement was assessed in BALB/c mice pre-supplemented with different dosages of cracked green algal (Haematococcus pluvialis) powder daily for 30 days. The supplemented mice were first tested over 8 days to find a hidden platform by swimming in a Morris water maze. Then, for 5 days, the mice were used to search for a visible platform in a Morris water maze. After that, the mice practised finding a safe place-an insulated platform in a chamber-for 2 days. During these animal experimental periods, similar algal meals containing astaxanthin at 0, 0.26, 1.3 and 6.4 mg/kg body weight were continuously fed to each group of tested mice. Profiles of latency, distance, speed and the direction angle to the platforms as well as the diving frequency in each group were measured and analyzed. The process of mice jumping up onto the insulated platform and diving down to the copper-shuttered bottom with a 36 V electrical charge were also monitored by automatic video recording. The results of the Morris maze experiment showed that middle dosage of H. pluvialis meals (1.3 mg astaxanthin/kg body weight) significantly shortened the latency and distance required for mice to find a hidden platform. However, there was no obvious change in swim velocity in any of the supplemented groups. In contrast, the visible platform test showed a significant increase in latency and swim distance, and a significant decrease in swim speed for all groups of mice orally supplemented with H. pluvialis powder compared to the placebo group (P < 0.05 or P < 0.01). Mice supplemented with the algal meal hesitantly turned around the original hidden platform, in contract to mice supplemented with placebo, who easily forgot the original location and accepted the visible platform as a new safe place. These results illustrate that astaxanthin-enriched H. pluvialis powder has the auxiliary property of memory improvement. The results from the platform diving test showed that the low and middle dosage of H. pluvialis powder, rather that the high dosage, increased the latency and reduced the frequency of diving from the safe insulated platform to the electrically stimulated copper shutter, especially in the low treatment group (P < 0.05). These results indicate that H. pluvialis powder is associated with dose-dependent memory improvement and that a low dosage of algal powder (<= middle treatment group) is really good for improving the memory.

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In this experiment, we tested the hypothesis that males of root voles (Microtus oeconomus Pallas) of different social ranks display different behavioural strategies. To document behavioural differences between social ranks, we investigated patterns in the behavioural responses to urine cues from familiar and novel individu in a choice maze. Ten pairs of male voles were efectively used in this experiment. All behaviour was recorded with OBSERVER 5.0. When experiment was finished, video tapes were transformed into digital data. Then all data were analyzed by SPSS. The results showed that the approach latency of subordinates was shorter for familiar odours than novel ones, dominant individuals preferentially entered the strange odourant box, subordinates preferred familiar odours over novel ones, subordinates spent more time visiting familiar odours compared to the novel odours, dominants preferred novel odours to familiar ones, subordinates approached familiar odours more frequently than novel ones and self-groomed more often in the familiar odourant box than in the novel box, and dominant and subordinate individuals showed significantly different countermarking behaviours to familiar and novel odours. In conclusion, the dominants and subordinates displayed different behaviour patterns when faced to familiar and novel conspecific males' urine cues. The data support our hypothesis that differences in social rank induce differences in behavioural patterns.