Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Centro Politécnico, Curitiba, PR, Brazil.
Prog Neuropsychopharmacol Biol Psychiatry. 2010 Oct 1;34(7):1229-35. doi: 10.1016/j.pnpbp.2010.06.025. Epub 2010 Jul 3.
Glucocorticoids play a role in memory formation, and they may contribute to memory changes in stress-related mental disorders, such as posttraumatic stress disorder. Cortisol may act through mineralocorticoid (MR) or glucocorticoid (GR) receptors, and the objective of the present study was to evaluate the effects of the MR antagonist spironolactone, the GR antagonist mifepristone, the MR agonist fludrocortisone, and the GR agonist dexamethasone on the extinction of contextually conditioned fear in rats. Propranolol was used as a positive control. As expected, propranolol administered before the test session increased memory extinction. Pre-test administration of spironolactone and low-dose dexamethasone also increased the extinction of an aversive memory, whereas fludrocortisone impaired extinction. High-dose dexamethasone and mifepristone were found to have no effect in this model. Post-test spironolactone treatment impaired aversive memory extinction. These results indicate that MR and GR are related to extinction of aversive memories, and MR blockade may be a promising candidate for the treatment of stress-related memory disorders.
糖皮质激素在记忆形成中起作用，它们可能导致与应激相关的精神障碍（如创伤后应激障碍）中的记忆改变。皮质醇可能通过盐皮质激素（MR）或糖皮质激素（GR）受体起作用，本研究的目的是评估 MR 拮抗剂螺内酯、GR 拮抗剂米非司酮、MR 激动剂氟氢可的松和 GR 激动剂地塞米松对大鼠情境条件性恐惧的消退的影响。普萘洛尔被用作阳性对照。正如预期的那样，测试前给予普萘洛尔可增加记忆消退。测试前给予螺内酯和低剂量地塞米松也可增加厌恶记忆的消退，而氟氢可的松则损害了消退。高剂量地塞米松和米非司酮在该模型中未发现有作用。测试后给予螺内酯治疗会损害厌恶记忆的消退。这些结果表明，MR 和 GR 与厌恶记忆的消退有关，MR 阻断可能是治疗与应激相关的记忆障碍的有前途的候选药物。
