β-Adrenoceptor Blockade in the Basolateral Amygdala, But Not the Medial Prefrontal Cortex, Rescues the Immediate Extinction Deficit
β-Adrenoceptor Blockade in the Basolateral Amygdala, But Not the Medial Prefrontal Cortex, Rescues the Immediate Extinction Deficit
复制标题
DOI：
10.1038/npp.2017.89
复制
发表时间：
2017-12-01
影响因子：
7.6
通讯作者：
Maren, Stephen
中科院分区：
文献类型：
--
作者：
Giustino, Thomas F.;Seemann, Jocelyn R.;Maren, Stephen
早期的心理干预，如暴露疗法，依靠消退学习来减少压力和创伤相关疾病的发展。然而，最近的研究表明，在创伤后不久进行的灭绝往往不能减少恐惧。这种即时灭绝缺陷（IED）可能是由于应激引起的与灭绝学习有关的神经回路失调。我们已经证明，用心得安阻断全身β -肾上腺素能挽救IED，但损害延迟消退。在这里，我们试图确定这些影响的神经轨迹。大鼠先进行听觉恐惧条件反射，然后接受立即（30分钟）或延迟（24小时）的灭绝训练。我们采用双侧脑内灌注心得安的方法，对内侧前额叶皮层（mPFC）或基底外侧杏仁核（BLA）的边缘下区进行脑内灌注，以检验β -肾上腺素能受体阻断对即时和延迟消退学习的影响。有趣的是，在bla内，而不是mpfc内，心得安拯救了IED；在立即灭绝之前，在bla内注射心得安的动物在灭绝恢复过程中表现出较少的自发恐惧恢复。重要的是，这不是由于条件反射记忆的巩固受损。相比之下，在bla和mpfc内，心得安对延迟消退学习没有影响。总的来说，这些数据有助于越来越多的文献表明，恐惧消退回路中关键节点的分离作用取决于相对于条件反射的消退时间。这些数据还表明，BLA中去肾上腺素能活性的升高是应激诱导的灭绝缺陷的基础。心得安可能是一个有用的辅助行为治疗干预最近创伤的个人谁是在发展的风险与创伤相关的障碍。
Early psychological interventions, such as exposure therapy, rely on extinction learning to reduce the development of stress-and trauma-related disorders. However, recent research suggests that extinction often fails to reduce fear when administered soon after trauma. This immediate extinction deficit (IED) may be due to stress-induced dysregulation of neural circuits involved in extinction learning. We have shown that systemic beta-adrenoceptor blockade with propranolol rescues the IED, but impairs delayed extinction. Here we sought to determine the neural locus of these effects. Rats underwent auditory fear conditioning and then received either immediate (30 min) or delayed (24 h) extinction training. We used bilateral intracranial infusions of propranolol into either the infralimbic division of the medial prefrontal cortex (mPFC) or the basolateral amygdala (BLA) to examine the effects of beta-adrenoceptor blockade on immediate and delayed extinction learning. Interestingly, intra-BLA, but not intra-mPFC, propranolol rescued the IED; animals receiving intra-BLA propranolol prior to immediate extinction showed less spontaneous recovery of fear during extinction retrieval. Importantly, this was not due to impaired consolidation of the conditioning memory. In contrast, neither intra-BLA nor intra-mPFC propranolol affected delayed extinction learning. Overall, these data contribute to a growing literature suggesting dissociable roles for key nodes in the fear extinction circuit depending on the timing of extinction relative to conditioning. These data also suggest that heightened noradrenergic activity in the BLA underlies stress-induced extinction deficits. Propranolol may be a useful adjunct to behavioral therapeutic interventions in recently traumatized individuals who are at risk for developing trauma-related disorders.