首页|条件恐惧大鼠消退保持与边缘下区磷酸化CREB的变化

条件恐惧大鼠消退保持与边缘下区磷酸化CREB的变化

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目的:探讨大鼠条件恐惧记忆在不同消退时间和消退后不同时间点,消退记忆保持与边缘下区磷酸化环磷酯腺苷反应元件(pCREB)的变化.方法:80只SD雄性成年大鼠随机分为:对照组(正常对照组、假训练A,B组、条件恐惧组);不同消退时间组(立即消退组、自然消退组、24 h消退组);消退后不同时间点组(将条件恐惧后24 h消退大鼠随机分为消退后1,3,7 d组),每组大鼠8只.大鼠条件恐惧由声音提示的条件刺激与不可逃避足底电击的非条件刺激配对建立.假训练A,B组给予声音和足底电击非配对刺激,仅有声音而无足底电击的消退训练于建模后15 min或24 h后进行;大鼠消退保持成绩和边缘下区pCREB表达测定于消退后24 h进行;而消退后1,3,7 d组分别在消退后第1,3,7 d测定.采用免疫组织化学和图像分析方法观察大鼠边缘下区pCREB的变化.结果:与不同消退时间组相比较,24 h消退组消退保持成绩(%)和pCREB表达数(个)均好于立即消退和自然消退组[(53±12),(820±106),P<0.01],立即消退与自然消退组组间差异比显著.假训练A组(20±7),B组(22±6)消退保持成绩最差;pcREB阳性表达数最少(432±97),(453±49)且组间无差异.与条件恐惧组相比较,消退后不同时间各组消退保持成绩、边缘下区pcREB阳性表达呈逐渐增加趋势(P<0.01);与消退后3 d组组间比较,消退后1,3 d组组间差异显著(P<0.01);与正常对照组(87±7),(994±31)相比较,条件恐惧大鼠消退保持、IL区pcREB表达显著降低[(37±11),(692±60),P<0.01].结论:边缘下区pCREB的表达水平与消退保持成绩正相关,条件恐惧建立后24 h进行恐惧消退的效果最好,消退后第1~3 d可能是决定条件性恐惧消退效果的关键时期.
Change of extinction retention and phosphorulated CREB in the rat infralimbic cortex after conditioned fear
AIM: To investigate the changes of extinction retention and expression of pCREB in rat's infralimbic cortex ( IL) at different regression time as well as at different time point after fear extinction. METHODS: Eighty male adult SD rats were randomly divided into control group (including conditioned fear group,shame A,B groups and normal control group),different regression time group(including natural extinction group,immediate extinction group and 24 h extinction group) and different time point after extinction group. Twenty-four hours fear extinction rats were randomly divided into extinction 1,3 and 7 d groups ( n = 8 ). The rats' conditioned fear was established by classical auditory fear con-ditioning(conditioned stimulus,CS) pairing with an aversive foot shock(unconditioned stimulus,US). Shame A and B groups were established by CS unpaired with US. Fear extinction training was performed with auditory indication but without foot shock in 15 min or 24 h after establishment of fear memory. Extinction retention test and expression of pCREB in IL were detected at 24 h after fear extinction and those in extinction 1,3 and 7 d groups were detected at 1st,3 rd and 7th day after extinction. The expressions of pCREB in IL were detected using immunohistochemistry and image analysis. RESULTS: The extinction retention ( % ) and expres- sion of pCREB in 24 h extinction group were better than those in natural extinction and immediate extinction groups [ ( 53 ± 12 ),(820 ± 106),P < 0. 01 ] and no statistical difference was found between natural extinction group and immediate extinction group. Shame A and B groups were lowest scored (20 ±7) and(22 ±6) and the expression of pCREB was most depressed (432 ± 97 ),(453 ±49),with no significant difference between groups. Compared with those in conditioned fear group,extinction retention scores and the number expression of pCREB in IL showed a gradual uptrend on 1st,3rd and 7th day after extinction (P < 0. 01 ). Compared with that in extinction 3 d group,difference between extinction 1 and 3 d groups was significant (P <0. 01 ). Compared with those in normal control group (87 ±7) and(994±31),the extinction retention and the expression of pCREB in IL in conditioned fear group remarkably decreased [ (37 ± 11),(692 ±60),P<0.01]. CONCLUSION: Expressions of pCREB in IL keep synchronized changes with the extinction retention score. Best effect is achieved in fear extinction 24 h after the establishment of conditioned fear. The 1st to the 3 rd day after the extinction may be the best therapeutic period.

fear/physiologyextinction retentioncerebral cortexpCREBrat

刘俊丽、王正洪、李敏、饶志仁

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第四军医大学训练部医学教育研究室,陕西,西安,710033

青海卫生职业技术学院,青海,西宁,810001

第三军医大学护理系心理学教研室,重庆,400038

第四军医大学基础部神经科学研究所,陕西,西安,710033

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恐惧/生理学 消退保持 大脑皮质 pCREB

国家自然科学基金

30670712

2009

第四军医大学学报
第四军医大学

第四军医大学学报

CSTPCDCSCD北大核心
影响因子:0.599
ISSN:1000-2790
年,卷(期):2009.30(11)
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