Roesler Rafael, Reolon Gustavo K, Maurmann Natasha, Schwartsmann Gilberto, Schröder Nadja, Amaral Olavo B, Valvassori Samira, Quevedo João
Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul Porto Alegre, Brazil ; Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul Porto Alegre, Brazil ; National Institute for Translational Medicine (INCT-TM) Porto Alegre, Brazil.
Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul Porto Alegre, Brazil ; National Institute for Translational Medicine (INCT-TM) Porto Alegre, Brazil ; Department of Internal Medicine, School of Medicine, Federal University of Rio Grande do Sul Porto Alegre, Brazil.
Front Behav Neurosci. 2014 Mar 17;8:91. doi: 10.3389/fnbeh.2014.00091. eCollection 2014.
Established fear-related memories can undergo phenomena such as extinction or reconsolidation when recalled. Extinction probably involves the creation of a new, competing memory trace that decreases fear expression, whereas reconsolidation can mediate memory maintenance, updating, or strengthening. The factors determining whether retrieval will initiate extinction, reconsolidation, or neither of these two processes include training intensity, duration of the retrieval session, and age of the memory. However, previous studies have not shown that the same behavioral protocol can be used to induce either extinction or reconsolidation and strengthening, depending on the pharmacological intervention used. Here we show that, within an experiment that leads to extinction in control rats, memory can be strengthened if rolipram, a selective inhibitor of phosphodiesterase type 4 (PDE4), is administered into the dorsal hippocampus immediately after retrieval. The memory-enhancing effect of rolipram lasted for at least 1 week, was blocked by the protein synthesis inhibitor anisomycin, and did not occur when drug administration was not paired with retrieval. These findings indicate that the behavioral outcome of memory retrieval can be pharmacologically switched from extinction to strengthening. The cAMP/protein kinase A (PKA) signaling pathway might be a crucial mechanism determining the fate of memories after recall.
已建立的与恐惧相关的记忆在被唤起时会经历诸如消退或重新巩固等现象。消退可能涉及创建一个新的、相互竞争的记忆痕迹，从而减少恐惧表达，而重新巩固可以介导记忆的维持、更新或强化。决定检索是否会引发消退、重新巩固或这两个过程都不引发的因素包括训练强度、检索时段的持续时间以及记忆的时长。然而，先前的研究并未表明，根据所使用的药理学干预措施，相同的行为方案可用于诱导消退、重新巩固或强化。在此我们表明，在导致对照大鼠出现消退的实验中，如果在检索后立即将4型磷酸二酯酶（PDE4）的选择性抑制剂咯利普兰注入背侧海马体，记忆可以得到强化。咯利普兰的记忆增强作用持续了至少1周，被蛋白质合成抑制剂茴香霉素阻断，并且当药物给药与检索不配对时不会出现这种作用。这些发现表明，记忆检索的行为结果可以通过药理学方法从消退转变为强化。环磷酸腺苷/蛋白激酶A（PKA）信号通路可能是决定回忆后记忆命运的关键机制。
