感觉门控的跨半球现象及其在吗啡成瘾过程中的应用研究
文献类型：学位论文
| 作者 | 郑佳威 |
| 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 | P50抑制 N100抑制 听觉诱发电位门控 同侧 对侧 大脑半球通路 正常被试 感觉门控 吗啡 依赖的建立 戒断 海马 多巴胺能的神经传递 大鼠 |
| 中文摘要 | 本论文的实验研究部分主要包括"正常被试同侧和对侧大脑半球通路听觉诱发电位门控的机制研究"和"吗啡依赖的建立和戒断过程中大鼠海马感觉门控（Sensorygating）的动态变化"。第一部分为了探讨感觉门控发生的神经生物学机制，在第一部分实验中，我们着重研究了感觉门控在同侧和对侧大脑半球的发生机制。感觉门控反映了大脑对听觉信息的加工处理过程。双声听诱发电位抑制模式在实验研究和临床方面已经广泛被用来评估感觉门控能力。当两个相同的声音刺激以500ms的时间间隔先后给予双耳时，第二个声音的听诱发电位P50成份的幅度会明显地受到第一个声音的抑制，这就是通常所说的P50抑制或是声诱发电位门控抑制。然而当这两个相同的声音刺激先后（也是500ms间隔）以相同方向（同侧）和不同方向（对侧）给予单侧耳朵时，感觉门控功能（表现为PSO前抑制和N100前抑制）是否能在同侧和对侧大脑半球之间发生是不清楚的。在本实验中，双耳双声刺激，同侧单耳双声刺激（包括左耳双声和右耳双声两种）和对侧单耳双声刺激（包括先右耳后左耳和先左耳后右耳两种）五种模式分别给予25个健康的正常被试者。同时在正常被试者的前额叶皮层（左侧和右侧）和颖叶皮层（左侧和右侧）四个脑区分别记录听觉诱发电位进而来评估P50和N100成份的抑制。实验结果显示：（1）P50和N100抑制（表现为T／C抑制比）在四个记录脑区和五种刺激模式下都没有性别之间的明显差异。（2）统计分析结果显示P50和N功O成份前抑制功能（表现为T／C抑制比）在四个记录的脑区没有明显差别。（3）五种不同的声音刺激模式对P50抑制功能（表现为T／C抑制比）具有显著性作用。具体表现为：在双侧双耳声刺激模式和同侧单耳双声刺激模式下，第二个声音诱发的P50成份的诱发电位幅度明显地受到第一个声音的抑制，即P50抑制发生；当相同的两个声音以对侧单耳双声刺激模式给予被试时，第二个声音诱发的PSO幅度很少受到第一个声音抑制，即P50抑制不发生。（4）正常被试声诱发电位N100成份在五种不同的声音刺激模式下都表现出正常的门控抑制（表现为T／C抑制比）并且相互之间没有统计学上的显著性差别。因此与P50成份不同，在对侧单耳双声刺激条件下较晚成份N100仍然具有正常的感觉门控能力。以上结果表明了，在标准的双耳双声刺激条件下N100成份具有和P50成份相似的门控抑制能力。另外，感觉门控（包括P50和N100抑制）能够在同侧大脑半球之间发生，这个结果意味着决定感觉门控的听觉通路可能以与调控双耳双声相似的方式调控同侧声音刺激。另一方面，较早成份P50抑制不能在对侧大脑半球之间发生，而与之相关的听觉通路却能够调控较晚成份N100抑制在对侧大脑半球之间发生。这可能是由于大脑半球之间的交叉联系在较长的时间里允许更多的听觉信息到达对侧半球而导致的。当前的实验结果可能反映了感觉门控在两侧大脑半球之间发生的某些特征。第二部分感觉门控可以"过滤"一些无关刺激进入以保护大脑免受干扰性信息的影响。听觉诱发电位抑制是常用来评估感觉「丁控能力的一种方法。由于感觉门控机制与边缘系统多巴胺的活动密切相关，并且门控能力很可能反映了吗啡成瘾过程中大脑状态。因此，在第二部分实验中，我们观察了在吗啡依赖的建立和戒断过程中吗啡对大鼠海马感觉门控（N4O成份）的影响作用。在实验中通过连续六天十二次（每天两次，间隔12小时）的盐酸吗啡腹腔注射使大鼠建立吗啡依赖，随后停止吗啡注射使大鼠处于自发的戒断阶段。在吗啡依赖的建立和戒断过程中检测海马感觉门控。而且，多巴胺DZ受体的拮抗剂氟派吮醇（haloPeridoD被用来检测多巴胺在吗啡弓｝起的海马感觉「1控变化中的作用。我们的结果显示出：（1）与对照组相比吗啡实验组在吗啡依赖的建立过程中海马感觉门控能力明显地被干扰；（2）氟派陡醇预处理作用会部分地恢复或逆转这个受损的（降低的）海马门控；（3）并且在连续地三天吗啡注射后，海马感觉门控受到损伤，表明了吗啡对海马门控的慢性作用；（4）与吗啡依赖阶段的结果相反，在吗啡戒断的第五天和第六天，吗啡实验组大鼠表现出明显提高的感觉门控。在吗啡依赖的建立和戒断过程中分别观察到的降低的和提高的海马感觉门控可能与海马结构的多巴胺神经传递活动有关。该实验结果与药物（包括吗啡）成瘾过程中多巴胺的神经传递活动的变化是一致的，同时也又进一步证明了多巴胺对感觉门控具有调控作用。最后，在吗啡成瘾过程中海马感觉门控的这种显著变化有力地表明了海马参与吗啡成瘾并暗示了海马与阿片类物质之间的相互作用。 |
| 英文摘要 | The research parts of this thesis include "Gating of auditory evoked potentials in ipsilateral and contralateral hemisphere pathways of healthy human subjects"(Part I) and "The dynamics of hippocampal sensory gating during the development of morphine dependence and withdrawal in rats" (Part II). Part I In the first part, we investigated the gating of auditory evoked potentials in ipsilateral and contralateral hemisphere pathways of healthy human subjects in order to give insights into the neural substrates of sensory gating. Sensory gating represents auditory information processing in the brain. The double clicks auditory evoked potential suppression paradigm has widely been used to assess the capabilities of sensory gating in experimental researches and clinical aspects. P50 component of the auditory evoked potentials was significantly suppressed by the first click when the two identical clicks (at 500ms interval) were presented to the binaural ears. Whereas the paired clicks (at the same time interval) were successively delivered to the same (ipsilaterally) and different (contralaterally) directions it is not yet clear that sensory gating functions (represented as P50 and N100 components) can occur across or within the ipsilateral and contralateral hemispheres. In present study, the binaural double clicks stimulation, ipsilaterally monaural double clicks stimulation (the double clicks to the left ear and the double clicks to the right ear) and contralaterally monaural double clicks stimulation (the first click to the right ear and the second click to the left ear; the first click to the left ear and the second click to the right ear) were respectively presented in the 25 healthy human subjects. Auditory evoked potentials (AEPs) were recorded in the prefrontal cortex (left and right) and the temporal cortex (left and right) to assess P50 and N1O0 gating. The results showed: (1) no significant differences between male and female were found in both four brain areas and five stimulation conditions; (2) statistical analysis showed that there were no significantly different brain structures effects on P50 and N100 suppression (representing T/C ratio); (3) P50 suppression (representing T/C ratio) was significantly different in five-stimulations paradigms. In detail, the P50 potential amplitude evoked by the second click was significantly suppressed or gated in binaural and ipsilateral stimulation paradigms (namely P50 suppression) whereas we found no evidence of P50 suppression in contralateral stimulation paradigm; (4) N100 evoked potential component exhibited normal gating (representing T/C ratio) in five different stimulation paradigms and there "were no significant differences in statistical Thus, different from P50 component, the later NlOO component still showed normal gating in contralateral stimulation condition. These results gave an evidence for NlOO component suppression similar to P50 suppression while the standard binaurally double clicks stimulation were presented. Sensory gating (P50 and NlOO suppression) could take effects cross the ipsilateral hemisphere. It strongly indicated that the auditory pathway which underling the sensory gating can modulate the ipsolateral auditory stimuli similar to the binaural stimuli. However, the earlier component P50 was not gated within the contralateral hemisphere whereas the later component NlOO suppression can occur and be modulated by the auditory pathway while the stimuli were presented contralaterally. It is possible due to the more auditory information reaching the contralateral hemisphere during the longer time by the interhemispheric connections. These results may reflect some aspects of the sensory gating occurring cross the interhemispheric pathway. Sensory gating can filter out the irrelevant stimuli in order to protect the brain from being flooded by the disruptive information. It is assessed in the double click auditory evoked potential suppression paradigm by measuring reduced responses to the second click compared to the first click presented 500ms apart. Because gating mechanisms are correlated with mesolimbic dopamine activity and may provide an index of the state of the brain in morphine addiction. In the second part, we investigated the effects of morphine on hippocampal sensory gating (N40 component) during the development of morphine dependence and during withdrawal. In present study, rats were made dependent upon morphine hydrochloride by a series of injections (every 12 h) over 6 days, followed by withdrawal after stopping morphine administration. Hippocampal gating was examined during the development of dependence and withdrawal. Moreover, the DA D2 receptor antagonist haloperidol was used to assess the contribution of dopamine to hippocampal gating induced by morphine. Our results showed: (1) the morphine-treated rats exhibited significantly disrupted hippocampal gating compared with the control rats during the development of morphine dependence; (2) Haloperidol pretreatment partially reversed this attenuated gating; (3) Moreover, after three days of morphine injections hippocampal gating was disrupted, suggesting a long-term effect of morphine on hippocampal suppression; (4) In contrast, there was significantly enhanced hippocampal gating at the fifth and sixth days of withdrawal The alternately decreased and enhanced hippocampal gating, observed during the development of morphine dependence and withdrawal, were probably associated with dopaminergic transmission in the hippocampus. The results are consistent with documented changes in dopaminergic neurotransmission during drug addiction and with the role of dopaminergic regulation in sensory gating. The dynamics of hippocampal gating during the development of morphine dependence and withdrawal suggests that the hippocampus structure is involved in the process of morphine addiction. It also indicates the interaction between the hippocampus and opioid. |
| 语种 | 中文 |
| 公开日期 | 2010-10-15 |
| 源URL | [http://159.226.149.42:8088/handle/152453/6290]  |
| 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 | 郑佳威. 感觉门控的跨半球现象及其在吗啡成瘾过程中的应用研究[D]. 北京. 中国科学院研究生院. 2005. |
入库方式： OAI收割
来源：昆明动物研究所
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