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题名	1. 大鼠眶额叶与吗啡成瘾关系的研究2.在自由活动的猕猴大脑上进行神经元单位记录方法的建立
作者	雷衍林
学位类别	博士
答辩日期	2005-05
授予单位	中国科学院研究生院
授予地点	北京
导师	马原野
关键词	吗啡 DADZ拮抗剂 DAD2激动剂 GAGAB受体 巴氯芬 损毁 药物依赖 眶额叶 大鼠 自由活动 微电极 神经元 单位放电记录
中文摘要	本论文的实验研究内容包括"大鼠眶额叶与吗啡成瘾关系的研究"及"在自由活动的称猴大脑上进行神经元单位放电记录方法的建立"两部分。第一部分在第一部分，着重探讨了眶额叶在吗啡诱导的心理成瘾中的作用。大量的研究证据表明，人类的眶额叶参与了强迫性的药物渴求行为。然而，我们不知道眶额叶在其中是起抑制作用还是促进作用？在人类，眶额叶的功能失调通常会打断动机化行为、不能预测后果以至不能进行正确地判断或者产生难以妙制的重复性行为，那么眶额叶的损伤对吗啡的奖赏效应以及吗啡诱导的药物依赖有什么影响呢？此外，DAD2受体的活动在吗啡成瘾中有十分重要的作用，那么眶额叶中DAD2受体的活动对吗啡诱导的心理成瘾的影响如何呢？另外，给动物或者人系统注射巴氯芬一GAB标受体的激动剂能缓解吗啡诱导的心理成瘾，那么眶额叶GAB绳受体的激活对吗啡诱导的心理成瘾是否具有抑制作用呢？因此，在第一部分我们以大鼠作为吗啡渴求的动物模型围绕上述三个问题开展实验工作。在第一部分的研究中，运用条件化位置偏好的模型，分别研究了大鼠眶额叶电损伤、大鼠眶额叶微量注射DAD2激动剂和拮抗剂以及GABAB受体激动剂一巴氯芬对吗啡诱导的药物依赖的影响；结果表明：（1）大鼠眶额叶在吗啡一环境刺激这个特殊的条件化学习过程中的作用是十分有限的；（2）如果条件化建立之后眶额叶的功能受损，可能导致眶额叶抑制功能的障碍，表现出抑制功能的减弱，因而不能抑制原来在一定的条件下引导的行为反应，所以，表现出对药物渴求的增加；长期滥用药物所导致眶额叶的功能受损势必会增加对药物的依赖。（3）眶额叶的DADZ受体可能对药物心理渴求起着抑制作用，当DAD2受体受到抑制时，眶额叶对吗啡渴求行为的抑制被削弱，导致动物渴求行为明显增加。同时，本研究也证实了眶额叶的GABAB受体活动没有涉及到对心理渴求的调节； 第二部分在第二部分，着重介绍了"在自由活动的称猴大脑上进行神经元单位放电记录方法的建立"。单个神经元活动的胞外记录是现代神经生物学研究的重要手段之一，是在细胞水平上研究大脑的感觉、运动、认知功能等常用而又极其重要的方法，它在研究动物脑与行为的关系上发挥着越来越重要的作用。然而，在传统的记录系统里记录设施通常限制着动物的活动，也影响了动物行为的自然展示，因而对动物脑功能与某些行为关系的研究具有很大的局限性。在传统技术的基础上，我们对神经元胞外记录方法进行了一系列的改进，建立起一套轻便的记录系统和适合在户外自由活动的琳猴大脑上进行神经元单位放电的胞外记录及追踪动物行为的方法。利用这种方法，就可以在室外自由活动称猴的大脑上记录到信噪比高且能稳定数小时的放电神经元；在单位放电的记录过程中，动物是处于室外自由活动状态不会因为实验操作引起动物的紧张；伴随着神经元单位放电的记录，同时进行着动物相关行为信息的记录；其中下列几个因素在方法的建立上起着至关重要的作用：（1）特殊设计的可移动的微电极；（2）小而轻的放大器；（3）信号的无线传输方式；它的建立为我们研究细胞活动和动物行为关系以及研究非人灵长类社会行为的细胞学基础提供了一种全新的方法。
英文摘要	The research parts of this thesis include "The effects of orbitofrontal cortex on morphine-induced drug dependence in rats"(Part I) and "Telemetric recordings of single neuron activity and visual scenes in monkeys walking in an open field"(Paxt II). Part I In this part, we investigated the effects of orbitofrontal cortex (OFC) on morphine-induced addiction. Several lines of evidence suggest that OFC contributes to compulsive drug seeking. However, we did not know whether the OFC would either facilitate or inhibit morphine-induced addiction. In people, dysfunction of OFC is associated with disturbances in motivation and an inability to anticipate consequences, leading to poor judgment and maladaptive behaviors that may depend in part on the conditioned reinforcement process. Then, we want to know the effects of electrolytic lesions of lateral OFC on the morphine-induced addiction. In addition, it is well known that DAD2 receptor plays a role important in mediating drug-induced addiction. Also, the effect of DA D2 receptors in the OFC on morphine-induced addition was unknown. Furthermore, evidence suggests that systemic administration of baclofen in morphine-dependent rats can attenuate the withdrawal signs. However, we did not know whether the activation of GABAB receptors in the OFC block or inhibit the incentive effects of morphine or morphine -induced craving. Based on above problems, our experiments were focused on these three topics in a rat model of addiction process. In this part, the effects of OFC lesions, microinjections of a GABAB receptor agonist-baclofen into OFC and microinjections of DA D2 agonist or antagoist into OFC on morphine-induced addiction were investigated using the conditioned place preference (CPP) paradigm in rats. First, the results indicate that OFC lesions before conditioning failed to prevent morphine-induced conditioned place preference, suggesting that OFC is not essential for associative learning between environmental cues and the hedonic experience of morphine. In contrast, OFC lesions after conditioning enhanced CPP, suggesting that OFC modulates the propensity for morphine seeking and the OFC plays a critical role in assessing the current motivational significance of drug-conditioned stimuli if stimulus-reward learning occurs before OFC lesions. Second, the results indicate that the DA D2 system in OFC modulates the propensity for morphine seeking and the decrease of the DA D2 system activities in OFC would enhance morphine -induced craving. Thirdly, it is concluded that activation of orbitofrontal cortex GABA B receptors involve in modulating the acute rewarding effects of morphine but not morphine -induced craving. Part II In the second part, we want to introduce how to develop the methods of telemetric recordings of single neuron activity and visual scenes in monkeys walking in an open field. Extracellular recording of the unit activities from a single neuron is a major and popular method in animals to study the sensory, motor and cognitive functions of the brain in cellular level and it plays a very important role in understanding the relationships of brain and behavior. However, with traditional recording systems some recording apparatus limit the area in which the subjects could walk and do not permit the manifestation of many natural behaviors; Thus, single unit recordings suffered from great limiting factors in the studies of the relationship of brain and behavior particularly in the studies of motor function. By modifying traditional recording systems we have developed a portable recording system and methods for obtainmg chronic recordings of single units and tracking rhesus monkey behavior in an open field. With this method, we are able to record the electrical activity of a single neuron that can last for several hours with high signal-noise ratio from the freely moving monkeys. During the entire recording process, monkey can move freely in the open field and thus minimized stress from the experiment. While the electrical activities for neurons were recorded, the animal behaviors were also monitored. In developing our method, several factors were important. These factors included designing (Da movable microelectrodes, (2) using a small and light amplifier, and (3) signals transmitted by a wireless system .The described methods provide a new way to examine correlations between single neuron activity and primate behaviors, and can also be used to study the cellular basis of social behaviors in non-human primates.
语种	中文
公开日期	2010-10-15
内容类型	学位论文
源URL	[http://159.226.149.42:8088/handle/152453/6265]
专题	昆明动物研究所_认知障碍病理学
推荐引用方式 GB/T 7714	雷衍林. 1. 大鼠眶额叶与吗啡成瘾关系的研究2.在自由活动的猕猴大脑上进行神经元单位记录方法的建立[D]. 北京. 中国科学院研究生院. 2005.

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