3,4-Methylenedioxymethamphetamine facilitates fear extinction learning.
3,4-Methylenedioxymethamphetamine facilitates fear extinction learning.
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DOI：
10.1038/tp.2015.138
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发表时间：
2015-09-15
影响因子：
6.8
通讯作者：
Howell LL
中科院分区：
文献类型：
--
作者：
Young MB;Andero R;Ressler KJ;Howell LL
急性给药的3，4-亚甲二氧基甲基苯丙胺（MDMA，'ecstasy'）已被提出与心理治疗相结合时，对创伤后应激障碍（PTSD）症状有长期的积极影响。没有临床前数据支持这些声明的机制基础。考虑到MDMA促进的心理治疗收益的持久性，我们假设MDMA改善了恐惧消退学习，这是PTSD基于创伤的治疗的关键过程。在这些实验中，小鼠首先暴露于暗示的恐惧条件反射，并在2天后的消退训练之前用药物载体或MDMA处理。MDMA是全身给药的，也直接针对已知会导致灭绝的大脑结构。除了灭绝的行为措施，脑源性神经营养因子（BDNF）和Fos的mRNA水平的变化进行了测量后，MDMA治疗和灭绝。MDMA（7.8 mg kg−1）在消退训练前给药时，持续且强烈地增强了长期消退。MDMA增加Fos在杏仁核和内侧前额叶皮质（mPFC）的表达，而BDNF的表达增加，只观察到在杏仁核后灭绝训练。当将MDMA（1 μg）直接注入杏仁核基底外侧复合体（BLA）时，可以重现灭绝增强作用，而当在灭绝前抑制脑源性神经营养因子信号传导时，增强作用就会消失。这些研究结果表明，MDMA通过BDNF依赖机制增强恐惧记忆消退，MDMA可能是PTSD和其他以恐惧学习改变为特征的焦虑症的基于创伤的治疗的有用辅助手段。
Acutely administered 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy') has been proposed to have long-term positive effects on post-traumatic stress disorder (PTSD) symptoms when combined with psychotherapy. No preclinical data support a mechanistic basis for these claims. Given the persistent nature of psychotherapeutic gains facilitated by MDMA, we hypothesized that MDMA improves fear extinction learning, a key process in exposure-based therapies for PTSD. In these experiments, mice were first exposed to cued fear conditioning and treated with drug vehicle or MDMA before extinction training 2 days later. MDMA was administered systemically and also directly targeted to brain structures known to contribute to extinction. In addition to behavioral measures of extinction, changes in mRNA levels of brain-derived neurotrophic factor (Bdnf) and Fos were measured after MDMA treatment and extinction. MDMA (7.8 mg kg−1) persistently and robustly enhanced long-term extinction when administered before extinction training. MDMA increased the expression of Fos in the amygdala and medial prefrontal cortex (mPFC), whereas increases in Bdnf expression were observed only in the amygdala after extinction training. Extinction enhancements were recapitulated when MDMA (1 μg) was infused directly into the basolateral complex of the amygdala (BLA), and enhancement was abolished when BDNF signaling was inhibited before extinction. These findings suggest that MDMA enhances fear memory extinction through a BDNF-dependent mechanism, and that MDMA may be a useful adjunct to exposure-based therapies for PTSD and other anxiety disorders characterized by altered fear learning.
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DOI：
10.1126/science.1214592
发表时间：
2011-12-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Karpova NN;Pickenhagen A;Lindholm J;Tiraboschi E;Kulesskaya N;Agústsdóttir A;Antila H;Popova D;Akamine Y;Bahi A;Sullivan R;Hen R;Drew LJ;Castrén E
通讯作者：
Castrén E
DOI：
10.1177/0269881110378371
发表时间：
2011-04
期刊：
Journal of psychopharmacology (Oxford, England)
影响因子：
--
作者：
Mithoefer MC;Wagner MT;Mithoefer AT;Jerome L;Doblin R
通讯作者：
Doblin R
影响因子：
3.2
作者：
Homberg JR
通讯作者：
Homberg JR
DOI：
10.3758/bf03209840
发表时间：
1994-08-01
期刊：
ANIMAL LEARNING & BEHAVIOR
影响因子：
--
作者：
BOUTON, ME;RICKER, ST
通讯作者：
RICKER, ST
影响因子：
16.2
作者：
LaBar, KS;Gatenby, JC;Phelps, EA
通讯作者：
Phelps, EA