Espejo Pablo Javier, Ortiz Vanesa, Martijena Irene Delia, Molina Victor Alejandro
IFEC-CONICET, Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
IFEC-CONICET, Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Neurobiol Learn Mem. 2017 Oct;144:166-173. doi: 10.1016/j.nlm.2017.06.004. Epub 2017 Jun 29.
It is well known that stress can affect mnemonic processes. In particular, stress before contextual fear conditioning induces a memory which exhibits resistance to being interfered with by Midazolam (MDZ) when applied after memory retrieval. Moreover, stress exposure strongly affects GABAergic transmission within the Basolateral Amygdala Complex (BLA), a brain structure critically involved in fear memory processing. The present study evaluated the involvement of GABAergic signaling within the BLA on the induction of resistance to memory reconsolidation interference. Results showed that MDZ administered intra-BLA before stress prevented the induction of resistance to the interfering effect of systemic administration of both MDZ and Propranolol on fear memory reconsolidation, when both applied after memory retrieval. The blockade of amygdala GABA-A receptors by the antagonist Bicuculline (BIC) before memory encoding induced resistance to interference by post-recall MDZ administration, similarly to that observed with stress exposure. Additionally, the systemic administration of d-cycloserine, a positive allosteric modulator of NMDA receptor, reverted the BIC-induced resistance to the MDZ interfering effect, in the same manner as that reported with stress-induced resistance. In summary, these results suggest that the GABAergic signaling in the BLA at the moment of memory encoding is determinant for the induction of fear memory resistance to the onset of the labilization/reconsolidation process.
众所周知，压力会影响记忆过程。特别是，情境恐惧条件反射前的压力会诱导出一种记忆，当在记忆提取后应用咪达唑仑（MDZ）时，这种记忆表现出对其干扰的抗性。此外，压力暴露会强烈影响基底外侧杏仁核复合体（BLA）内的GABA能传递，BLA是一个在恐惧记忆处理中起关键作用的脑结构。本研究评估了BLA内GABA能信号传导在诱导对记忆再巩固干扰的抗性中的作用。结果表明，在压力前向BLA内注射MDZ可防止对全身注射MDZ和普萘洛尔对恐惧记忆再巩固干扰作用产生抗性的诱导，这两种药物均在记忆提取后应用。在记忆编码前用拮抗剂荷包牡丹碱（BIC）阻断杏仁核GABA - A受体可诱导出对回忆后MDZ给药干扰的抗性，这与压力暴露时观察到的情况类似。此外，NMDA受体的正变构调节剂d - 环丝氨酸的全身给药以与压力诱导抗性相同的方式逆转了BIC诱导的对MDZ干扰作用的抗性。总之，这些结果表明，记忆编码时BLA中的GABA能信号传导对于诱导恐惧记忆对不稳定/再巩固过程开始的抗性起决定性作用。
