ISSN 0439-755X
CN 11-1911/B
主办:中国心理学会
   中国科学院心理研究所
出版:科学出版社

心理学报 ›› 2021, Vol. 53 ›› Issue (6): 603-612.doi: 10.3724/SP.J.1041.2021.00603

• 研究报告 • 上一篇    下一篇

普萘洛尔修复即刻消退产生的二次创伤

王红波1, 邢小莉1, 王慧颖2,3()   

  1. 1河南大学认知、脑与健康研究所, 教育科学学院, 河南省心理与行为研究所, 开封 475004
    2新乡医学院第二附属医院, 河南省精神病医院, 新乡 453002
    3河南省生物精神病学重点实验室, 新乡医学院, 新乡 453002
  • 收稿日期:2020-11-09 发布日期:2021-04-25
  • 通讯作者: 王慧颖 E-mail:wanghuiyingwing@foxmail.com
  • 基金资助:
    教育部人文社会科学研究项目(20YJC190019);河南省生物精神病学重点实验室开放课题(ZDSYS2019009);河南省医学科技攻关计划联合共建项目(2018020375)

Propranolol rescued secondary trauma induced by immediate extinction

WANG Hongbo1, XING Xiaoli1, WANG Huiying2,3()   

  1. 1Institute of Cognition, Brain and Health; School of Educational Science; Henan Key Lab of Psychology and Behavior, Henan University, Kaifeng 475004, China
    2Henan Mental Hospital, the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang 453002, China
    3Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang 453002, China
  • Received:2020-11-09 Published:2021-04-25
  • Contact: WANG Huiying E-mail:wanghuiyingwing@foxmail.com

摘要:

恐惧消退能力的受损是创伤后应激障碍(posttraumatic stress disorder, PTSD)的标志之一。以往的研究表明, 相较于延迟消退, 恐惧获得后短时间内进行的消退训练不能形成长时程的消退记忆, 这一现象被称为即刻消退缺损。然而, 目前并不清楚这种缺损是一次性的, 还是会继续影响其后的重消退。实验1中, 大鼠在恐惧习得后1小时(即刻消退)或24小时(延迟消退)开始进行消退训练, 24小时后进行重消退, 再24小时后进行消退记忆的测试。结果显示, 与延迟消退相比, 即刻消退效果缺损, 并引起第二天的重消退也出现效果缺损。实验2中, 恐惧获得后立即给予大鼠盐水或β-肾上腺素受体阻断剂普萘洛尔(10 mg/kg, i.p.), 然后测试即刻消退和重消退的效果。结果显示, 普萘洛尔虽没有阻止即刻消退的缺损, 但避免了重消退出现缺损。总之, 严重创伤后的即刻消退不但无法有效抑制恐惧反应, 还可能造成二次创伤, 会损害恐惧消退能力, 而普萘洛尔可修复即刻消退引起的重消退缺损。这些结果将有助于我们加深对PTSD病理机制和早期干预后果的认识。

关键词: 条件性恐惧, 即刻消退缺损, 重消退, β-肾上腺素受体阻断剂, 普萘洛尔

Abstract:

One hallmark of posttraumatic stress disorder (PTSD) involves impairments in the ability to extinguish conditioned fear memory. Accumulating evidence suggests that extinction training that occurs shortly after fear conditioning is less effective than delayed extinction training in yielding long-term extinction memory, a phenomenon that is referred to as immediate extinction deficit (IED). However, unknown is whether the IED is just an aberration or continues to affect re-extinction.

This study revealed that the early extinction intervention after severe trauma may not only fail to inhibit the fear response but also act as a secondary trauma which can continually damage the ability to extinguish fear memory. Propranolol may be a good candidate to repair such damage. Our findings improve our understanding of the pathogenesis of PTSD and outcomes of an early intervention and may be helpful for selecting appropriate and effective interventions after trauma exposure and avoid secondary trauma that is caused by the intervention itself.

In Experiment 1, 32 Sprague-Dawley rats were randomly divided into four groups (Immediate-Extinction, Immediate-No Extinction, Delayed-Extinction, Delayed-No Extinction) and underwent a standard fear conditioning procedure in which they received five tone-footshock trials in chamber A. After either 1 h (immediate) or 24 h (delayed), half of the animals underwent 30 extinction trials (1st extinction session) in chamber B where the tone was presented alone. The other half remained in chamber B without any tone or footshock (these animals served as a no-extinction control group). Twenty-four hours later, these rats underwent the 2nd extinction session (re- extinction) in chamber B. Twenty-four hours after the 2nd extinction session, the rats were once again returned to chamber B and tested for their fear response to four continuous tones. The fear response was assessed by freezing behavior, and the effect of the 1st extinction session was assessed by the average freezing response across the first four trials of the 2nd extinction session. Compared with rats in the delayed extinction group, recently conditioned rats exhibited significantly higher levels of fear in the 2nd extinction session, although an equivalent decline in freezing was observed in both groups across the 1st extinction session, suggesting that immediate extinction failed to maintain fear suppression the next day. Furthermore, after undergoing two extinction training sessions, rats in the immediate extinction group exhibited no significant reduction of freezing compared with the non-extinguished control during the retention test, suggesting that the deficit reappeared during re-extinction.

The aim of Experiment 2 was to investigate whether the deficit that was induced by immediate extinction could be rescued by the β-adrenergic receptor antagonist propranolol. In Experiment 2, 20 Sprague-Dawley rats underwent the same procedures as the immediate extinction groups in Experiment 1, with the exception that they received saline or propranolol (10 mg/kg, i.p.) within minutes after fear conditioning. We found that one injection of propranolol immediately after fear acquisition rescued the deficit of re-extinction but not immediate extinction.

Key words: fear conditioning, immediate extinction deficit, re-extinction, β-noradrenergic receptor antagonist, propranolol

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