Department of Clinical Psychology, Amsterdam, The Netherlands.; Amsterdam Brain and Cognition, University of Amsterdam, Amsterdam, The Netherlands.
Department of Clinical Psychology, Amsterdam, The Netherlands.; Amsterdam Brain and Cognition, University of Amsterdam, Amsterdam, The Netherlands..
Biol Psychiatry. 2015 Dec 15;78(12):880-6. doi: 10.1016/j.biopsych.2015.04.006. Epub 2015 Apr 14.
Although disrupting the process of memory reconsolidation has a great potential for clinical practice, the fear-amnesic effects are typically demonstrated through Pavlovian conditioning. Given that older and stronger memories are generally more resistant to change, we tested whether disrupting reconsolidation would also diminish fear in individuals who had developed a persistent spider fear outside the laboratory.
Spider-fearful participants received a single dose of 40 mg of the noradrenergic β-blocker propranolol (n = 15), double-blind and placebo-controlled (n = 15), after a short 2-min exposure to a tarantula. To test whether memory reactivation was necessary to observe a fear-reducing effect, one additional group of spider-fearful participants (n = 15) received a single dose of 40 mg propranolol without memory reactivation.
Disrupting reconsolidation of fear memory transformed avoidance behavior into approach behavior in a virtual binary fashion-an effect that persisted at least 1 year after treatment. Interestingly the β-adrenergic drug did initially not affect the self-declared fear of spiders but instead these reports followed the instant behavioral transformation several months later.
Our findings are in sharp contrast with the currently pharmacological and cognitive behavioral treatments for anxiety and related disorders. The β-adrenergic blocker was only effective when the drug was administered upon memory reactivation, and a modification in cognitive representations was not necessary to observe a change in fear behavior. A new wave of treatments that pharmacologically target the synaptic plasticity underlying learning and memory seems to be within reach.
尽管干扰记忆再巩固过程在临床实践中有很大的潜力,但恐惧性健忘的效果通常是通过巴甫洛夫条件反射来证明的。鉴于较旧和较强的记忆通常更能抵抗变化,我们测试了在实验室之外已经形成持久蜘蛛恐惧的个体中,干扰再巩固是否也会减少恐惧。
蜘蛛恐惧的参与者在短暂的 2 分钟暴露于狼蛛后,接受单次剂量为 40 毫克的去甲肾上腺素能β阻断剂普萘洛尔(n = 15),双盲和安慰剂对照(n = 15)。为了测试是否需要记忆再激活来观察到减少恐惧的效果,另一组蜘蛛恐惧的参与者(n = 15)接受单次剂量 40 毫克普萘洛尔而不进行记忆再激活。
恐惧记忆的再巩固干扰以虚拟二进制方式将回避行为转化为接近行为——这种效果至少在治疗后 1 年持续存在。有趣的是,β-肾上腺素能药物最初并没有影响对蜘蛛的自我恐惧,而是在几个月后随着即时行为转变而出现这些报告。
我们的发现与目前焦虑和相关障碍的药理学和认知行为治疗形成鲜明对比。只有在药物在记忆再激活时给药时,β-肾上腺素能阻滞剂才有效,并且不需要改变认知表现就可以观察到恐惧行为的变化。似乎可以通过药理学靶向学习和记忆的突触可塑性来实现一波新的治疗方法。