Noradrenergic Stimulation Impairs Memory Generalization in Women
Noradrenergic Stimulation Impairs Memory Generalization in Women
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DOI：
10.1162/jocn_a_01118
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发表时间：
2017-07-01
影响因子：
3.2
通讯作者：
Schwabe, Lars
中科院分区：
文献类型：
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作者：
Kluen, Lisa Marieke;Agorastos, Agorastos;Schwabe, Lars
记忆泛化对于适应性决策和行动至关重要。我们对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。近期的证据表明，压力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压力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，健康的男性和女性在完成一项探究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 - 肾上腺素受体拮抗剂育亨宾，或者两种药物。药物未影响学习表现。然而，育亨宾导致女性出现显著的泛化受损，但男性没有。反过来，氢化可的松对男性和女性的记忆泛化都没有影响。目前的研究结果表明，去甲肾上腺素能活动增加，但不是皮质醇，足以以性别特异性的方式破坏记忆泛化，这对以泛化缺陷为特征的与压力相关的精神障碍具有相关意义。
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 mediatorsnoradrenaline and glucocorticoidsis sufficient to disrupt memory generalization. In a double-blind, placebo-controlled design, healthy men and women received orally a placebo, hydrocortisone, the 2-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.