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文拉法辛对大鼠听觉恐惧记忆消退的影响

The effects of venlafaxine on the extinction of fear memory in rat

摘要目的 采用条件性恐惧记忆消退模型研究文拉法辛对恐惧消退记忆获得以及巩固阶段的影响.方法 实验大鼠在A环境接受听觉恐惧记忆训练,给予不同剂量文拉法辛腹腔注射后在B环境进行恐惧记忆消退训练和测试,观察药物对恐惧消退记忆的作用.结果 重复测量ANOVA分析组间消退不动时间百分比,测试条件( Pre-C,Post-C,Post-T) (F2,44 =458.958,P<0.001)、文拉法辛剂量(0,20,40 mg/kg)( F2,22 =43.026,P<0.001)、二者交互作用(F4,44=31.363,P<0.001);组内消退post hoc比较显示3组大鼠获得CS的恐惧记忆无差异;消退训练结束时3组大鼠均已消退,各剂量组间均无差异(P>0.05);消退训练之前30min腹腔注射高剂量文拉法辛(40 mg/kg)促进恐惧记忆组间消退,但不影响组内消退,中剂量(20 mg/kg)易化作用不显著.结论 文拉法辛可以促进恐惧记忆的消退,这种易化作用存在剂量依赖关系.对创伤后应激障碍和惊恐障碍等疾病的恐惧焦虑情绪的治疗具有一定的临床指导价值.

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abstractsObjective To identify the effects of venlafaxiue on the acquisition and consolidation of fear extinction memory in conditioning fear memory extinction model.Methods Male Sprague-Dawley rats were treated with fear conditioning training in the A environment.Before the extinction training,all the experimental rats were given different doses of venlafaxine intraperitoneal injection.After 24 hours,all the rats test in the B environment.Results Repeated-measures ANOVA were conducted on the percent of freezing time for between-session extinction,test condition (F2,44 =458.958,P<0.001 ) and VEN dose(F2,22 =43.026,P<0.001 ) and a Test condition * Treatment interaction (F4,44 =31.363,P < 0.001 ).For the within-session,post hoc comparisons indicated that the three groups that received different dose of VEN (0,20 and 40 mg/kg) did not differ from each other (P > 0.05 ),indicating similar extinction following the post-conditioning.The rats injected with high-dose venlafaxine (40 mg/kg) intraperitoneally before extinction training showed pro,motion of between-subjects extinction of fear memory,but does not affect the within-subjects extinction.There was no significant catabolism in the rats injected with middle-dose (20 mg/kg).Conclusion The available date indicate that venlafaxine could promote the extinction of fear memory and there is a dose-dependent relationship of venlafaxine in the facilitation of fear memory.Our results could provide some clinical guidance for the treatment of post-traumatic stress disorder and panic disorder.

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DOI 10.3760/cma.j.issn.1674-6554.2012.10.004
发布时间 2012-12-17(万方平台首次上网日期,不代表论文的发表时间)
基金项目
国家自然科学基金(81071085)
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