Parr Lisa A, Brooks Jenna M, Jonesteller Trina, Moss Shannon, Jordano James O, Heitz Thomas R
Yerkes National Primate Research Center, 954 Gatewood Rd., Atlanta, GA, 30329, USA; Department of Psychiatry and Behavioral Science, Emory University, Atlanta, GA, 30322, USA; Center for Translational Social Neuroscience, Emory University, Atlanta, GA, 30329, USA.
Yerkes National Primate Research Center, 954 Gatewood Rd., Atlanta, GA, 30329, USA.
Psychoneuroendocrinology. 2016 Dec;74:149-157. doi: 10.1016/j.psyneuen.2016.08.028. Epub 2016 Aug 31.
Studies in a variety of species have reported enhanced prosocial effects after an acute administration of the neuromodulating hormone, oxytocin (OT). Although the exact mechanisms underlying these effects are not fully understood, there is broad interest in developing OT into a treatment for social deficits. Only a few studies, however, have examined the effects of OT if given repeatedly during early development, the period when early intervention is likely to have the greatest benefits for reversing the progression towards social impairment. Those studies, exclusively in rodents, report mixed results. Some have shown enhancement of prosocial behavior, including increased social exploration, but others have shown anti-social effects, including increased aggression. In the present study, infant rhesus macaques were treated with a high-frequency (3× per week) or low-frequency (1× per week) dose of intranasal oxytocin (IN-OT) or placebo (IN-saline) between two and six months of age, after which their reactions to dynamic facial expressions (neutral, lipsmacking and threats) were measured. Results showed that IN-OT, compared to placebo, increased the time monkeys spent viewing the expression videos, but selectively reduced attention to the eyes in neutral faces in a dose dependent manner. The mechanism for this non-prosocial effect may be that repeated IN-OT administration down-regulates the expression of OT receptors in brain regions important for regulating social attention. Consequently, our results raise questions about the efficacy of implementing chronic IN-OT as a pharmacotherapy for the treatment of social deficits, particularly if given early in development. More work is needed, not only to identify optimal treatment schedules, but also to understand how IN-OT exerts its influences on the brain and behavior.
对多种物种的研究报告称,急性给予神经调节激素催产素(OT)后,亲社会效应增强。尽管这些效应背后的确切机制尚未完全了解,但人们对将OT开发成治疗社交缺陷的药物有着广泛的兴趣。然而,只有少数研究考察了在早期发育期间(即早期干预可能对逆转社交障碍进展产生最大益处的时期)反复给予OT的效果。那些研究仅在啮齿动物中进行,结果不一。一些研究显示亲社会行为增强,包括社交探索增加,但另一些研究则显示出反社会效应,包括攻击性增加。在本研究中,对2至6个月大的恒河猴婴儿给予高频(每周3次)或低频(每周1次)剂量的鼻内催产素(IN-OT)或安慰剂(IN-生理盐水),之后测量它们对动态面部表情(中性、咂嘴和威胁)的反应。结果显示,与安慰剂相比,IN-OT增加了猴子观看表情视频的时间,但以剂量依赖的方式选择性地减少了对中性面孔中眼睛的关注。这种非亲社会效应的机制可能是反复给予IN-OT会下调对调节社会注意力很重要的脑区中OT受体的表达。因此,我们的结果对将慢性IN-OT作为治疗社交缺陷的药物疗法的疗效提出了疑问,特别是如果在发育早期给予。不仅需要更多工作来确定最佳治疗方案,还需要了解IN-OT如何对大脑和行为产生影响。