Kluen Lisa Marieke, Agorastos Agorastos, Wiedemann Klaus, Schwabe Lars
1 University of Hamburg.
2 University Clinic Hamburg-Eppendorf.
J Cogn Neurosci. 2017 Jul;29(7):1279-1291. doi: 10.1162/jocn_a_01118. Epub 2017 Mar 2.
Memory generalization is essential for adaptive decision-making and action. Our ability to generalize across past experiences relies on medial-temporal lobe structures, known to be highly sensitive to stress. Recent evidence suggests that stressful events may indeed interfere with memory generalization. Yet, the mechanisms involved in this generalization impairment are unknown. We tested here whether a pharmacological elevation of major stress mediators-noradrenaline and glucocorticoids-is sufficient to disrupt memory generalization. In a double-blind, placebo-controlled design, healthy men and women received orally a placebo, hydrocortisone, the α2-adrenoceptor antagonist yohimbine that leads to increased noradrenergic stimulation, or both drugs, before they completed an associative learning task probing memory generalization. Drugs left learning performance intact. Yohimbine, however, led to a striking generalization impairment in women, but not in men. Hydrocortisone, in turn, had no effect on memory generalization, neither in men nor in women. The present findings indicate that increased noradrenergic activity, but not cortisol, is sufficient to disrupt memory generalization in a sex-specific manner, with relevant implications for stress-related mental disorders characterized by generalization deficits.
记忆泛化对于适应性决策和行动至关重要。我们跨过去经历进行泛化的能力依赖于内侧颞叶结构，已知该结构对压力高度敏感。最近的证据表明，应激事件可能确实会干扰记忆泛化。然而，这种泛化受损所涉及的机制尚不清楚。我们在此测试了主要应激介质——去甲肾上腺素和糖皮质激素的药理学升高是否足以破坏记忆泛化。在一项双盲、安慰剂对照设计中，健康男性和女性在完成一项探索记忆泛化的联想学习任务之前，口服安慰剂、氢化可的松、导致去甲肾上腺素能刺激增加的α2肾上腺素能拮抗剂育亨宾或两种药物。药物并未影响学习表现。然而，育亨宾导致女性出现明显的泛化受损，但男性未出现。相反，氢化可的松对男性和女性的记忆泛化均无影响。目前的研究结果表明，去甲肾上腺素能活性增加而非皮质醇足以以性别特异性方式破坏记忆泛化，这对以泛化缺陷为特征的应激相关精神障碍具有重要意义。
