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慢性吗啡暴露长时程戒断导数认知灵活性损伤的相关脑区活性分析
Alternative TitleAlterations in brain activation in rasponse to prolonged morphine withdrwal-induced behavioral inflexibilitly in rats
刘田娥
Subtype硕士
Thesis Advisor梁璟
2018-06
Degree Grantor中国科学院大学
Place of Conferral中国科学院心理研究所
Degree Name理学硕士
Degree Discipline健康心理学
Keyword吗啡戒断 反转学习 眶额叶 内侧前额叶 纹状体
Abstract

良好的认知灵活性能够让人和动物保持思想和动作的灵活变化,以适应周围环境的改变,是个体生存和物种繁衍的必要前提。强迫性用药行为是药物成瘾的核心表现。这种强迫样行为的存在可能是成瘾药物暴露导致认知灵活性损伤的结果。因此,强迫性用药行为的神经基础可能是,成瘾药物的长期暴露诱发了相关脑区的功能改变,而这些脑区参与认知灵活性调控。本研究通过采用行为药理学和免疫组织化学等实验方法,探索吗啡慢性暴露对于大鼠认知灵活性的影响,并分析与这种认知损伤相关的多个脑区活性的变化。

首先, 我们对大鼠进行两周的慢性递增剂量吗啡腹腔注射(开始剂量18.9mg/kg, 每日递增3.9mg/kg,直至69.6mg/kg ),之后分别在戒断2周(短期戒断)和6周(长期戒断)后,采用反转学习任务模式对大鼠的认知灵活性进行评估分析。结果显示,只有长期戒断的动物出现了反转学习能力的损伤,吗啡暴露之后的短期戒断未影响大鼠的反转学习能力。随后,在反转学习任务完成之后,我们使用c-Fos免疫荧光组织化学分析的方法对短期和长期戒断的动物(包括盐水对照组及吗啡实验组)的15个脑区的神经元活性进行了比较分析。结果显示,长期戒断动物的眶额叶脑区(orbitofrontal cortex, OFC )(包括中部、外侧及腹侧)活性明显降低;背内侧纹状体(dorsomedial striatum, DMS)及内侧前额叶( medial prefrontal cortex, mPFC)活性明显升高;而背外侧纹状体(dorsolateral striatum, DLS )、伏隔核(nucleus accumbens, NAc )、杏仁核(amygdala )、丘脑室旁核(paravcntricular thalamic nucleus)及运动皮层(motor cortex)没有变化。然而,这15个脑区在短期戒断后未呈现出神经元活性的显著变化。综上,我们的研究结果提示,慢性大剂量吗啡暴露后的动物在长期戒断后呈现出认知灵活性的损伤,其中额叶皮质以及纹状体的异常活性变化可能是这种损伤的神经基础。

Other Abstract

Normal cognitive flexibility is the ability to maintain the flexibility of thought and action to adapt the changes in environment, and it is essential for individual survival and species reproduction. We all know that compulsive drug-use is a critical feature of drug addiction, and compulsive behavior may be linked to the behavior inflexibility that is caused by drug addiction. Therefore, the alternation in brain activation in response to the chronic drug exposure may be the neurological basis for compulsive drug addiction. In the present study, by using behavioral pharmacology and immunochemistry, we investigated the effects of chronic morphine exposure on cognitive inflexibility in rats, and analyzed the alternation in brain activities, which was associated with altered cognitive flexibility.

First, the rats were subjected to two-week morphine/saline exposure The rats in the morphine group received chronic escalating-dose injections (beginning at 18.9mg/kg and increasing by 3.9 mg/kg until 69.6mg/kg, i.p.). The saline group administered saline injection. Then, we analyzed the effects of chronic morphine exposure on reversal learning after 2-weck (short-term) and 6-week (prolonged) morphine withdrawal. We found that only prolonged morphine withdrawal impaired reversal learning and no effect after short-term withdrawal. We further compared the level of neuronal activation using cFos immunohistochemistry in 15 brain areas between rats that underwent morphine withdrawal and saline-control rats after a test of reversal learning. The results revealed that rats exhibited impairments in reversal learning presented a significant decrease in cFos expression in the orbitofrontal cortex (OFC), including the medial, lateral, and ventral OFC. cFos expression significantly increased in the dorsomedial striatum and major subregions of the medial prefrontal cortex (mPFC) in the morphine group. Rats that underwent prolonged morphine withdrawal exhibited no significant changes in cFos expression in the dorsolateral striatum, nucleus accumbens, amygdala, paraventricular thalamic nucleus, or motor cortex. The rats that underwent short-term withdrawal did not present any changes in cFos expression in any of these brain regions.

In conclusion, cognitive infexibility may be induced after prolonged morphine withdrawal, and it may be caused by the alternation of neuronal activation in the prefrontal cortex and dorsomedial striatum.

Pages36
Language中文
Document Type学位论文
Identifierhttp://ir.psych.ac.cn/handle/311026/28857
Collection健康与遗传心理学研究室
Recommended Citation
GB/T 7714
刘田娥. 慢性吗啡暴露长时程戒断导数认知灵活性损伤的相关脑区活性分析[D]. 中国科学院心理研究所. 中国科学院大学,2018.
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