Neurochemical evidence for differential effects of acute and repeated oxytocin administration
Neurochemical evidence for differential effects of acute and repeated oxytocin administration
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DOI：
10.1038/s41380-018-0249-4
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发表时间：
2021-02-01
影响因子：
11
通讯作者：
Yamasue, Hidenori
中科院分区：
文献类型：
--
作者：
Benner, Seico;Aoki, Yuta;Yamasue, Hidenori
急性给药和重复给药在催产素的行为效应上的差异表明了不同的潜在神经生物学机制。目前的研究采用了人类临床试验和动物研究相结合的方法，比较了急性和重复给予催产素引起的神经化学变化。人类研究通过使用H-1磁共振波谱分析内侧前额叶代谢物水平，这是我们的随机、双盲、安慰剂对照交叉试验的次要结果，该试验对17名患有自闭症谱系障碍的无精神药物的高功能男性进行了6周的鼻腔给药(48IU/天)和安慰剂受试者设计。成年雄性C57BL/6J小鼠一次性注射催产素或生理盐水(200 ng/100亩L/鼠，n=12)或连续14天(200 ng/100亩L/鼠/天，n=16)后，分析其额叶内侧前额叶转录表达水平。结果表明，与急性催产素不同，重复应用催产素显著降低了前额内侧N-乙酰天冬氨酸(P=0.043)和谷氨酸-谷氨酰胺(GLX；P=0.001)水平。这些下降与催产素在社会判断任务中引起的内侧前额叶功能核磁共振活动的改善成反比和特异性相关(对于NAA，r=0.680，p=0.004；对于Glx，r=0.491，p=0.053)，而不是与服用安慰剂期间的变化有关。在野生型小鼠中，我们发现反复给予催产素降低了额叶内侧N-甲基-d-天冬氨酸受体2B的转录表达(p=0.018)，而不同于急性催产素，它改变了与催产素(p=0.0004)和神经活动(p=0.0002)相关的转录表达。本研究结果提示，谷氨酸能系统对催产素重复给药的独特敏感性可能解释了催产素在急性给药和重复给药之间的不同行为效应。
A discrepancy in oxytocin's behavioral effects between acute and repeated administrations indicates distinct underlying neurobiological mechanisms. The current study employed a combination of human clinical trial and animal study to compare neurochemical changes induced by acute and repeated oxytocin administrations. Human study analyzed medial prefrontal metabolite levels by using H-1-magnetic resonance spectroscopy, a secondary outcome in our randomized, double-blind, placebo-controlled crossover trial of 6 weeks intranasal administrations of oxytocin (48 IU/day) and placebo within-subject design in 17 psychotropic-free high-functioning men with autism spectrum disorder. Medial prefrontal transcript expression levels were analyzed in adult male C57BL/6J mice after intraperitoneal injection of oxytocin or saline either once (200 ng/100 mu L/mouse, n = 12) or for 14 consecutive days (200 ng/100 mu L/mouse/day, n = 16). As the results, repeated administration of oxytocin significantly decreased the medial prefrontal N-acetylaspartate (NAA; p = 0.043) and glutamate-glutamine levels (Glx; p = 0.001), unlike the acute oxytocin. The decreases were inversely and specifically associated (r = 0.680, p = 0.004 for NAA; r = 0.491, p = 0.053 for Glx) with oxytocin-induced improvements of medial prefrontal functional MRI activity during a social judgment task not with changes during placebo administrations. In wild-type mice, we found that repeated oxytocin administration reduced medial frontal transcript expression of N-methyl-d-aspartate receptor type 2B (p = 0.018), unlike the acute oxytocin, which instead changed the transcript expression associated with oxytocin (p = 0.0004) and neural activity (p = 0.0002). The present findings suggest that the unique sensitivity of the glutamatergic system to repeated oxytocin administration may explain the differential behavioral effects of oxytocin between acute and repeated administration.