Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Farmacología, IFEC-CONICET, Córdoba, Argentina.
Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Farmacología, IFEC-CONICET, Córdoba, Argentina.
Prog Neuropsychopharmacol Biol Psychiatry. 2019 Mar 8;89:9-15. doi: 10.1016/j.pnpbp.2018.08.018. Epub 2018 Aug 24.
A 1-day fear memory in ethanol withdrawn (ETOH) rats is resistant to destabilization-reconsolidation process. However, d-cycloserine (DCS) reverts this disturbance. Considering that the formation of pathological fear memories in humans often occurs long time before the requirement of an intervention, the study of older memories is relevant in ETOH rats. In addition, the resistance to destabilization and DCS effect on this memory phase at molecular level in ETOH rats have not been corroborated yet. Firstly, we examined the effect of a pharmacological intervention after reactivation on reconsolidation of a 7-day fear memory in ETOH rats. Then, and considering that enhanced GluN2B expression and ubiquitin-proteasome system (UPS) activity are involved in destabilization, we evaluated them following reactivation in ETOH rats. Furthermore, DCS effect on such destabilization markers was examined. It was found that the pharmacological intervention after reactivation did not affect the 7-day fear memory in ETOH rats with DCS reversing this resistance. Memory reactivation increased GluN2B expression, polyubiquitination levels and proteasome activity in the basolateral amygdala complex (BLA) of control (CON) rats only; without affecting these molecular events in ETOH rats. Finally, ETOH rats treated with DCS and CON animals displayed elevated and similar UPS activities in the BLA after reactivation. In conclusion, the reactivation of an older fear memory formed during ethanol withdrawal does not trigger the molecular events associated with destabilization, and DCS facilitates this memory phase by enhancing the UPS activity.
在乙醇戒断（ETOH）大鼠中，1 天的恐惧记忆对失稳-再巩固过程具有抗性。然而，D-环丝氨酸（DCS）可逆转这种干扰。鉴于人类病理性恐惧记忆的形成通常发生在需要干预之前很久，因此在 ETOH 大鼠中研究较旧的记忆是相关的。此外，尚未在 ETOH 大鼠中证实失稳对该记忆阶段的影响以及 DCS 对该记忆阶段的分子水平的影响。首先，我们研究了在 ETOH 大鼠中重新激活后药物干预对 7 天恐惧记忆再巩固的影响。然后，考虑到增强的 GluN2B 表达和泛素-蛋白酶体系统（UPS）活性与失稳有关，我们在 ETOH 大鼠中评估了它们在重新激活后的情况。此外，还研究了 DCS 对这种失稳标志物的影响。结果发现，重新激活后的药物干预不会影响 ETOH 大鼠的 7 天恐惧记忆，而 DCS 可逆转这种抗性。记忆再激活仅增加了对照组（CON）大鼠的外侧杏仁核复合体（BLA）中 GluN2B 表达、多泛素化水平和蛋白酶体活性；而对 ETOH 大鼠没有影响。最后，用 DCS 治疗的 ETOH 大鼠和 CON 动物在重新激活后在 BLA 中显示出升高且相似的 UPS 活性。总之，在乙醇戒断期间形成的较旧恐惧记忆的再激活不会引发与失稳相关的分子事件，而 DCS 通过增强 UPS 活性促进了这一记忆阶段。
