标准化-重新整合,这依赖于检索,被认为是减轻创伤记忆消极方面的机会。基于再巩固阻断的治疗策略被认为比依赖于记忆灭绝的当前疗法更有效。然而,极度紧张的记忆经常被证明对这个过程有抵抗力。这里,在通过强烈的恐惧条件诱导小鼠强大的恐惧记忆后,我们根据广泛性恐惧(GF)的程度,研究了使其对药理学调节敏感的可能性。为了实现这一点,我们建立了GF的有序梯度,由关联上下文(CA)和非关联上下文(CB,CC,CD,和CE)到令人厌恶的事件。我们观察到,随着暴露环境与CA变得不那么相似,在雄性和雌性小鼠中,防御模式从被动行为转变为主动行为。随后,在有条件的动物中,我们在暴露于不同环境后给予普萘洛尔(CA,CB,CC,CD或CE)。在男性中,在暴露于CA或CB后,普萘洛尔治疗可减少冻结时间并增强风险评估行为,但不是在CC之后,CD,或CE,与对照组相比。在女性中,普萘洛尔暴露于CC后观察到类似的行为模式变化,但不是在其他上下文之后。这些结果突显了通过控制回忆过程中的泛化水平来间接操纵强大的上下文恐惧记忆的可能性。此外,事实证明,普萘洛尔对再巩固的作用不会导致恐惧记忆本身的减少,而是它的重组导致更大的行为灵活性(从被动行为到主动行为)。最后,从临床角度来看,这将具有相当大的相关性,因为遵循这一策略可以使与创伤性记忆形成相关的精神疾病的治疗更有效,压力更小.
Labilization-reconsolidation, which relies on retrieval, has been considered an opportunity to attenuate the negative aspects of traumatic memories. A therapeutic strategy based on reconsolidation blockade is deemed more effective than current therapies relying on memory extinction. Nevertheless, extremely stressful memories frequently prove resistant to this process. Here, after inducing robust fear memory in mice through strong fear conditioning, we examined the possibility of rendering it susceptible to pharmacological modulation based on the degree of generalized fear (GF). To achieve this, we established an ordered gradient of GF, determined by the perceptual similarity between the associated context (CA) and non-associated contexts (CB, CC, CD, and CE) to the aversive event. We observed that as the exposure context became less similar to CA, the defensive pattern shifted from passive to active behaviors in both male and female mice. Subsequently, in conditioned animals, we administered propranolol after exposure to the different contexts (CA, CB, CC, CD or CE). In males, propranolol treatment resulted in reduced freezing time and enhanced risk assessment behaviors when administered following exposure to CA or CB, but not after CC, CD, or CE, compared to the control group. In females, a similar change in behavioral pattern was observed with propranolol administered after exposure to CC, but not after the other contexts. These results highlight the possibility of indirectly manipulating a robust contextual fear memory by controlling the level of generalization during recall. Additionally, it was demonstrated that the effect of propranolol on reconsolidation would not lead to a reduction in fear memory per se, but rather to its reorganization resulting in greater behavioral flexibility (from passive to active behaviors). Finally, from a clinical viewpoint, this would be of considerable relevance since following this strategy could make the treatment of psychiatric disorders associated with traumatic memory formation more effective and less stressful.