Intranasal oxytocin is receiving increasing research attention as a potential treatment for several brain disorders due to promising preclinical results. However, translating these findings to humans has been hampered by remaining uncertainties about its pharmacodynamics and the methods used to probe its effects in the human brain. Using a dose-response design (9, 18 and 36 IU) and a novel administration device, we demonstrate that oxytocin-induced physiological changes in the amygdala at rest, a key-hub of the brain oxytocin system, follow a dose-response curve with maximal effects for lower doses. Yet, the effects of oxytocin vary by amygdala subdivision, highlighting the need to qualify dose-response curves within subregion. We further link physiological changes with the density of the oxytocin receptor gene mRNA across brain regions, strengthening our confidence in intranasal oxytocin as a valid approach to engage central targets. Finally, we demonstrate that intranasal oxytocin does not disrupt cerebrovascular reactivity; the absence of major vascular confounds corroborates the validity of haemodynamic neuroimaging to probe the effects of intranasal oxytocin in the human brain.

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少即是多：人脑中鼻内催产素药效学的剂量反应

由于有希望的临床前结果，鼻内催产素作为多种脑部疾病的潜在治疗方法正受到越来越多的研究关注。然而，将这些发现转化为人类一直受到对其药效学和用于探测其在人脑中作用的方法的不确定性的阻碍。使用剂量反应设计（9、18和36 IU）和新型给药装置，我们证明了催产素诱导的杏仁扁桃体静止状态（大脑催产素系统的关键枢纽）中的生理变化遵循剂量反应曲线最低剂量时效果最佳。然而，催产素的作用因杏仁核细分而异，突显了需要对次区域内的剂量反应曲线进行限定。我们进一步将生理变化与整个大脑区域的催产素受体基因mRNA的密度联系起来，增强我们对鼻内催产素的信心，使之成为参与中心目标的有效方法。最后，我们证明了鼻内催产素不会破坏脑血管反应性。缺乏主要血管混杂物，证实了血流动力学神经成像技术探测鼻内催产素在人脑中的作用的有效性。