Freeman Sara M, Samineni Sridhar, Allen Philip C, Stockinger Diane, Bales Karen L, Hwa Granger G C, Roberts Jeffrey A
California National Primate Research Center, University of California-Davis, Davis, CA 95616, USA.
Valley Biosystems, Inc., West Sacramento, CA 95605, USA.
Psychoneuroendocrinology. 2016 Apr;66:185-94. doi: 10.1016/j.psyneuen.2016.01.014. Epub 2016 Jan 18.
Oxytocin (OT) is a neuropeptide that mediates a variety of complex social behaviors in animals and humans. Intranasal OT has been used as an experimental therapeutic for human conditions characterized by deficits in social functioning, especially autism spectrum disorder and schizophrenia. However, it is currently under intense debate whether intranasal delivery of OT reaches the central nervous system. In this study, four female rhesus macaques were implanted with chronic intrathecal catheters and used to investigate the pharmacokinetic profile of OT in the central nervous system and the peripheral vasculature following intravenous (IV) and intranasal (IN) administration of OT. In a randomized, crossover design, OT was given to four awake monkeys at three different doses based on body weight (0.1 IU/kg; 1 IU/kg; 5 IU/kg). A time course of concurrent cerebrospinal fluid (CSF) and plasma samples were taken following administration. We found a dose-dependent effect of IV OT treatment on plasma OT levels, which peaked at 5 min post-dose and gradually returned to baseline by 120 min. In contrast, a change in CSF OT was only observed at the highest IV dose (5 IU/kg) at 15 min post-dose and gradually returned to baseline by 120 min. After IN administration, there was no significant change in plasma OT at any of the three doses. However, at the highest dose level, we found a significant increase in CSF OT at 15-30 min post- dose. The results of this study in light of recent, similar publications highlight the importance of methodological consistency across studies. This study also establishes a non-human primate model that can provide a stable platform for carrying out serial sampling from the central nervous system and peripheral vasculature concurrently.
催产素（OT）是一种神经肽，可介导动物和人类的多种复杂社会行为。鼻内催产素已被用作一种实验性治疗方法，用于治疗以社交功能缺陷为特征的人类疾病，尤其是自闭症谱系障碍和精神分裂症。然而，目前关于鼻内给药的催产素是否能到达中枢神经系统存在激烈争论。在本研究中，四只雌性恒河猴植入慢性鞘内导管，用于研究静脉注射（IV）和鼻内（IN）给予催产素后，催产素在中枢神经系统和外周血管系统中的药代动力学特征。在随机交叉设计中，根据体重给四只清醒的猴子给予三种不同剂量的催产素（0.1 IU/kg；1 IU/kg；5 IU/kg）。给药后同时采集脑脊液（CSF）和血浆样本的时间进程。我们发现静脉注射催产素治疗对血浆催产素水平有剂量依赖性影响，在给药后5分钟达到峰值，并在120分钟时逐渐恢复到基线水平。相比之下，仅在最高静脉注射剂量（5 IU/kg）下，给药后15分钟观察到脑脊液催产素变化，并在120分钟时逐渐恢复到基线水平。鼻内给药后，在任何三种剂量下血浆催产素均无显著变化。然而，在最高剂量水平下，我们发现给药后15 - 30分钟脑脊液催产素显著增加。结合近期类似出版物来看，本研究结果凸显了各研究方法一致性的重要性。本研究还建立了一种非人灵长类动物模型，可为同时从中枢神经系统和外周血管系统进行系列采样提供稳定平台。
