Dose-dependent effects of estrogen on prediction error related neural activity in the nucleus accumbens of healthy young women
Dose-dependent effects of estrogen on prediction error related neural activity in the nucleus accumbens of healthy young women
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DOI：
10.1007/s00213-019-05409-7
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发表时间：
2020-03-01
影响因子：
3.4
通讯作者：
Sommer，Tobias
中科院分区：
文献类型：
--
作者：
Bayer，Janine;Rusch，Tessa;Sommer，Tobias
基本原理虽然性类固醇 17-β-雌二醇 (E2) 对伏隔核 (NAc) 中多巴胺能 (DA) 传递的影响在雌性大鼠中得到充分证明，但在人类中的研究却不一致。此外，已经观察到E2对海马可塑性的影响呈线性和倒U形剂量反应曲线，但E2对NAc影响的剂量反应曲线的形状特征却少得多。目的研究E2对人NAc中DA相关神经活动的影响的剂量反应曲线。方法口服给予安慰剂或E2戊酸2、4、6或12 mg剂量采用随机、双盲设计，连续两天对 125 名处于低激素月经期的年轻女性进行自然循环。 E2治疗方案诱导了广泛的E2水平，从生理水平（2毫克组和4毫克组；相当于周期峰值）到超生理水平（6毫克组和12毫克组；相当于妊娠早期）。这使得研究 E2 对 NAc 活性影响的不同剂量反应函数成为可能。在 E2 高峰期间，参与者执行了完善的逆向学习范式。我们使用通过计算强化学习模型估计的试验预测误差（PE）作为多巴胺能活动的代理。计算了根据唾液 E2 水平预测 PE 相关 NAc 活性的线性和二次回归分析。结果 PE 相关 NAc 活性与唾液 E2 增加之间存在正线性关系。结论随机、安慰剂控制的 E2 水平升高刺激人脑中的 NAc 活性，可能是由多巴胺能过程介导的。
RationaleWhereas the effect of the sex steroid 17-beta-estradiol (E2) on dopaminergic (DA) transmission in the nucleus accumbens (NAc) is well evidenced in female rats, studies in humans are inconsistent. Moreover, linear and inverted u-shaped dose response curves have been observed for E2’s effects on hippocampal plasticity, but the shape of dose response curves for E2’s effects on the NAc is much less characterized.ObjectivesInvestigation of dose response curves for E2’s effects on DA-related neural activity in the human NAc.MethodsPlacebo or E2 valerate in doses of 2, 4, 6 or 12 mg was orally administered to 125 naturally cycling young women during the low-hormone menstruation phase on two consecutive days using a randomized, double-blinded design. The E2 treatment regimen induced a wide range of E2 levels, from physiological (2- and 4-mg groups; equivalent to cycle peak) to supraphysiological levels (6- and 12-mg groups; equivalent to early pregnancy). This made it possible to study different dose response functions for E2’s effects on NAc activity. During E2 peak, participants performed a well-established reversal learning paradigm. We used trial-wise prediction errors (PE) estimated via a computational reinforcement learning model as a proxy for dopaminergic activity. Linear and quadratic regression analyses predicting PE-related NAc activity from salivary E2 levels were calculated.ResultsThere was a positive linear relationship between PE-associated NAc activity and salivary E2 increases.ConclusionsThe randomized, placebo-controlled elevation of E2 levels stimulates NAc activity in the human brain, likely mediated by dopaminergic processes.