Department of Psychology, Texas A&M University, College Station, TX, USA.
Institute for Neuroscience, Texas A&M University, College Station, TX, USA.
Neuropsychopharmacology. 2017 Dec;42(13):2537-2544. doi: 10.1038/npp.2017.89. Epub 2017 May 2.
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 β-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 β-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.
早期的心理干预，如暴露疗法，依赖于消退学习来减少应激和创伤相关障碍的发展。然而，最近的研究表明，在创伤后不久进行消退治疗时，消退往往无法减少恐惧。这种即时消退缺陷（IED）可能是由于应激诱导的与消退学习相关的神经回路失调所致。我们已经表明，用普萘洛尔进行系统的β-肾上腺素受体阻断可以挽救 IED，但会损害延迟消退。在这里，我们试图确定这些效应的神经定位。大鼠接受听觉恐惧条件反射，然后接受即时（30 分钟）或延迟（24 小时）消退训练。我们使用双侧内侧前额叶皮层（mPFC）下边缘或基底外侧杏仁核（BLA）的脑内注射普萘洛尔，以检查β-肾上腺素受体阻断对即时和延迟消退学习的影响。有趣的是，BLA 内而非 mPFC 内的普萘洛尔挽救了 IED；在即时消退前接受 BLA 内普萘洛尔的动物在消退检索过程中表现出较少的恐惧自发恢复。重要的是，这不是由于条件记忆的巩固受损。相比之下，BLA 内和 mPFC 内的普萘洛尔均不影响延迟消退学习。总体而言，这些数据为越来越多的文献提供了支持，表明在消退相对于条件作用的时间方面，恐惧消退回路中的关键节点具有不同的作用。这些数据还表明，BLA 中的去甲肾上腺素活性升高是应激诱导的消退缺陷的基础。普萘洛尔可能是对最近遭受创伤且易患创伤相关障碍的个体进行行为治疗干预的有用辅助手段。
