Reference Centre for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità (ISS), Viale Regina Elena 299, I-00161, Rome, Italy.
Department of Neurosciences, Istituto Superiore di Sanità (ISS), Viale Regina Elena 299, I-00161, Rome, Italy.
Neuropharmacology. 2018 Dec;143:250-267. doi: 10.1016/j.neuropharm.2018.09.010. Epub 2018 Sep 10.
Deficits in empathy, the ability to share an emotion of another individual, constitute a hallmark of several psychopathological conditions, including conduct disorder. The co-occurrence of excess rates of aggression, general violation of societal norms and callous-unemotional traits confers specific risk for adult psychopathy. In the present study, we relied on a recently devised experimental model of conduct disorder in mice to test the potential efficacy of intranasal oxytocin administration. Two subgroups of BALB/cJ male mice exhibiting opposite profiles in emotional contagion (i.e. socially transmitted adoption of another's emotional states) underwent a series of tests mapping onto reactive aggression, information processing, perseverative behaviour, punishment-related emotional memory, physiological arousal and hormonal stress reactivity, with or without intranasal oxytocin administration (5.0 or 20.0 μg/kg). Collectively, our data indicate that a trait of markedly reduced emotional contagion is associated with a behavioural syndrome of sensorimotor gating deficits, impaired emotional memory, increased aggression and stereotyped behaviours, dysregulations in the circadian rhythms of activity and body temperature and dampened physiological reactivity to external stressors. Moreover, in the absence of changes in oxytocin receptor density in the neural network involved in empathy-like behaviour, we showed that oxytocin administration normalised emotional contagion, aggression and behavioural stereotypies, thereby ameliorating the phenotype of mice characterised by deficient empathy-like behaviour. Besides, oxytocin led to a lower, more prolonged neuroendocrine response of the HPA-axis to stress in all mice. Ultimately, current data support the notion that oxytocin may constitute a valid therapeutic approach in disturbances characterised by abnormal aggression and excess callousness.
同理心缺陷,即分享他人情感的能力缺陷,是包括品行障碍在内的多种精神病理学的标志。攻击性过剩、普遍违反社会规范和无情特质的共同存在,使个体具有成年精神变态的特定风险。在本研究中,我们依赖于最近设计的一种小鼠品行障碍实验模型,来测试鼻内给予催产素的潜在疗效。两组 BALB/cJ 雄性小鼠表现出相反的情感传染(即社会传递另一个人的情绪状态)特征,进行了一系列测试,以映射到反应性攻击、信息处理、持续性行为、与惩罚相关的情绪记忆、生理唤醒和激素应激反应,同时或不进行鼻内催产素给药(5.0 或 20.0μg/kg)。总的来说,我们的数据表明,情感传染的显著降低特征与感觉运动门控缺陷、情绪记忆受损、攻击性增加和刻板行为、活动和体温昼夜节律失调以及对外源性应激源的生理反应减弱的行为综合征相关。此外,在参与共情样行为的神经网络中,催产素受体密度没有变化的情况下,我们表明催产素给药可使情感传染、攻击和行为刻板正常化,从而改善共情样行为缺陷小鼠的表型。此外,催产素导致所有小鼠的 HPA 轴对压力的神经内分泌反应更低、更持久。最终,目前的数据支持催产素可能是一种有效的治疗方法的观点,可用于治疗以异常攻击和过度无情为特征的障碍。