Pruessner Jens C, Champagne Frances, Meaney Michael J, Dagher Alain
McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, Canada H3A 2B4.
J Neurosci. 2004 Mar 17;24(11):2825-31. doi: 10.1523/JNEUROSCI.3422-03.2004.
Mesolimbic dopamine is thought to play a role in the processing of rewards. However, animal studies also demonstrate dopamine release in response to aversive stressful stimuli. Also, in animal studies, disruptions of the mother-infant relationship have been shown to have long-lasting effects on the mesolimbic dopamine system and the hypothalamic-pituitary adrenal axis. We therefore investigated dopamine release in response to stress in human subjects, considering the relationship to early life parental care. We screened 120 healthy young college students for parental care in early life using a combination of telephone interviews and questionnaires. Five students from the top end and five students from the bottom end of the parental care distribution were then invited for a positron emission tomography study using [11C]raclopride and a psychosocial stress task. The psychosocial stressor caused a significant release of dopamine in the ventral striatum as indicated by a reduction in [11C]raclopride binding potential in the stress versus resting condition in subjects reporting low parental care. Moreover, the magnitude of the salivary cortisol response to stress was significantly correlated with the reduction in [11C]raclopride binding in the ventral striatum (r = 0.78), consistent with a facilitating effect of cortisol on dopamine neuron firing. These data suggest that aversive stressful events can be associated with mesolimbic dopamine release in humans, and that the method presented here may be useful to study the effects of early life events on neurobiological stress systems.
中脑边缘多巴胺被认为在奖赏处理过程中发挥作用。然而，动物研究也表明，厌恶应激刺激会引发多巴胺释放。此外，在动物研究中，母婴关系的破坏已被证明会对中脑边缘多巴胺系统和下丘脑 - 垂体 - 肾上腺轴产生长期影响。因此，考虑到与早期生活中父母照顾的关系，我们研究了人类受试者对应激的多巴胺释放情况。我们通过电话访谈和问卷调查相结合的方式，对120名健康的年轻大学生早期生活中的父母照顾情况进行了筛查。然后，从父母照顾分布的高端选取5名学生，从低端选取5名学生，邀请他们使用[11C]雷氯必利进行正电子发射断层扫描研究，并完成一项社会心理应激任务。社会心理应激源导致腹侧纹状体中多巴胺显著释放，这在报告父母照顾水平低的受试者中表现为应激状态与静息状态相比[11C]雷氯必利结合潜力降低。此外，唾液皮质醇对应激的反应幅度与腹侧纹状体中[11C]雷氯必利结合的降低显著相关（r = 0.78），这与皮质醇对多巴胺神经元放电的促进作用一致。这些数据表明，厌恶应激事件可能与人类中脑边缘多巴胺释放有关，并且这里介绍的方法可能有助于研究早期生活事件对神经生物学应激系统的影响。
