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孤束核基底外侧杏仁核通路在诱发吗啡奖赏记忆再巩固中的作用
Alternative TitleRole of the nucleus of the solitary tract projections to the basolateral amygdala in the induction of morphine associated memo ry re co nsolidation
郑伟
Subtype硕士
Thesis Advisor隋南, 张建军
2020-06
Degree Grantor中国科学院心理研究所
Place of Conferral中国科学院心理研究所
Degree Name理学硕士
Degree Discipline应用心理学
Keyword再巩固 基底外侧杏仁核 孤束核 蓝斑 吗啡 成瘾记忆
Abstract

研究目的:成瘾记忆长期存在是用药环境诱发渴求和复吸的内在原因。再巩固是记忆提取后的一个不稳定的阶段,期间成瘾记忆易被破坏从而抑制复吸。但是,因为再巩固难被诱发,使其应用受到了很大限制。有研究表明基底外侧杏仁核( basolateral amygdala BLA )是成瘾奖赏记忆再巩固的关键脑区,且 BLA中激活神经元数目越多,再巩固越容易被破坏。 BLA 接受来自孤束核( nucleus of the solitary tract NTS )和蓝斑 locus coeruleus LC )的投射,但是再巩固 的诱发中,这两条通路是否 能易化 BLA 神经元的激活尚不清楚。

研究方案:为了研究N TS B LA 和 LC BLA 这两条神经通路 在诱发 成瘾 记忆再巩固中的作用, 本研究应用大鼠吗啡自给药 self administration S A 范式,进行了如下实验: 1 明确 吗啡与用药线索共同暴露 诱发吗啡 S A 记忆的 再巩固2 明确诱发吗啡 SA 记忆再巩固 所 激活的 BLA 相关 脑区及 神经通 路 3 )验证NTS BLA 和 L C BLA 在诱发吗啡 S A 记忆再巩固中的作用。

研究结果:1 与 单独线索暴露( condition stimuli CS 相比 ,吗啡与线索共同暴露( uncondition stimuli, US+CS 更易于诱发吗啡 SA 记忆的再巩固2 与 CS 暴露相比, US+CS 暴露激活了更多的 BLA 和 NTS (而非 LC )中的神经元3 在 CS 暴露的同时,采用 光遗传和 化学遗传 学方法 激活 NTS BLA 通路(而非LC BLA 通路)能够诱发吗啡 SA 记忆的再巩固; 4 在 US+CS 暴露的同时,采用化学遗传方法抑制NTS BLA通路(而非 LC BLA 通路)能够抑制再巩固的诱发。

研究结论:本研究发现NTS BLA (而非 LC BLA )神经通路的激活是 US+CS诱发吗啡奖赏记忆再巩固的必要条件表明吗啡奖赏记忆再巩固的诱发可能存在特异的神经通路基础 。 提示在暴露于用药相关线索的同时,如能刺激 NTS 或 BLA可能有助于促进再巩固的诱发为拓展干预再巩固在临床上的应用提供了新的实验证据。

Other Abstract

Objectives: Drug related memory contributes to the chronic relapse problem. This persistent memory can be transiently destabilized by memory retrieval, after which memories are reconsolidated. Duringreconsolidation,manipulations can be given to impair drug related memory, leading to thesuppression ofrelapse.However, its applicability is restricted becauseofthe reconsolidation-resistant boundary conditions,whichconstrain the initial memory destabilization. Considerable evidence demonstrates that neuronal activation in the basolateral amygdala (BLA)is crucial for drug reward memory reconsolidation. Moreover, the BLA receives projections from the nucleus of the solitary tract (NTS) and the locus coeruleus(LC). However, the specific neural circuits underlying this induction ofreconsolidationremain essentially unknown.

Methods: To study the role of afferent projections into theBLAin the inductionof drug memoryreconsolidation,weusing the morphine self-administration (SA) paradigmand performing threeexperiments: 1) Define retrieval parameters that could induce reconsolidationof morphine SA memory;2) Determine the effect of different memory retrievals on neuronal activation in the BLA, the NTS andtheLC; 3)Determine the effect of activation/inhibition of NTS-BLA or LC-BLA on the reconsolidationof morphine SA memory.

Results: 1) Morphine (unconditioned stimulus, US) + morphine associated conditioned stimuli (CS) exposure, rather than CS exposure, induced reconsolidation of morphine SA memory ; C ompared with CS exposure, US + CS exposure induces more neurons acti vation in the BLA and the NTS, but not in the LC 3 NTS BLA but not LC BLA activation during CS retrieval induced reconsolidation 4) NTS BLA but not LC BLA inactivation during memory retrieval prevented memory reconsolidation induced by US + CS exposure.

Conclusion: Taken together, our results identify a specific neural circuit underlie the transformation of a stable opiate related memory into an unstable memory and subsequently guiding reconsolidation. Clinically, addicts were always exposed to the drug related clues to induce the reconsolidation. Thus, our findings suggested that the stimulation of the NTS or the BLA during the exposure time may promote the induction.

Pages53
Language中文
Document Type学位论文
Identifierhttp://ir.psych.ac.cn/handle/311026/33920
Collection健康与遗传心理学研究室
Recommended Citation
GB/T 7714
郑伟. 孤束核基底外侧杏仁核通路在诱发吗啡奖赏记忆再巩固中的作用[D]. 中国科学院心理研究所. 中国科学院心理研究所,2020.
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