Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada.
Neurosciences & Mental Health, The Hospital for Sick Children, 555 University Ave., M5G 1X8, Toronto, Ontario, Canada.
Prog Neuropsychopharmacol Biol Psychiatry. 2022 Dec 20;119:110604. doi: 10.1016/j.pnpbp.2022.110604. Epub 2022 Jul 14.
The glucocorticoid receptor (GR) forms a protein complex with FKBP51 that is increased in post-traumatic stress disorder (PTSD) and by fear conditioned learning. Disrupting the GR-FKBP51 complex with a synthetic peptide can block the storage or retrieval of fear conditioned memories, which could be a novel approach to the alleviate fear associated memory in PTSD. However, a potential unacceptable side effect could be the impairment of other types of memory. Thus, we investigated the effect of disrupting the GR-FKBP51 complex on recognition memory using the novel object and displaced object recognition tasks, spatial memory in the Morris water maze, and on social interaction in Crawley's three-chamber social interaction test. We did not observe adverse effects on these other types of memory and conclude that the GR-FKBP51 interaction remains a promising target for treating psychiatric disorders characterized by unwanted aversive memories such as in PTSD.
糖皮质激素受体（GR）与 FKBP51 形成蛋白质复合物，这种复合物在创伤后应激障碍（PTSD）和恐惧条件性学习中增加。用合成肽破坏 GR-FKBP51 复合物可以阻止恐惧条件记忆的存储或检索，这可能是一种减轻 PTSD 中与恐惧相关记忆的新方法。然而，一个潜在的不可接受的副作用可能是对其他类型记忆的损害。因此，我们使用新物体和移动物体识别任务、莫里斯水迷宫中的空间记忆以及克劳利三腔社交互动测试中的社交互动来研究破坏 GR-FKBP51 复合物对识别记忆的影响。我们没有观察到对这些其他类型记忆的不良影响，并得出结论，GR-FKBP51 相互作用仍然是治疗以不愉快的厌恶记忆为特征的精神障碍的有前途的靶点，例如 PTSD。
