Brake W G, Noel M B, Boksa P, Gratton A
Douglas Hospital Research Centre, McGill University, Department of Psychiatry, Montréal, Canada.
Neuroscience. 1997 Apr;77(4):1067-76. doi: 10.1016/s0306-4522(96)00543-x.
Evidence from animal studies suggests that a period of anoxia to the fetus, a consequence common to many birth complications, results in long-term alterations in ventral mesencephalic dopamine function. Long-term functional changes in these dopamine neurons, in particular those that innervate the nucleus accumbens, also occur when animals are repeatedly stressed. In the present study, we examined the possibility that a period of anoxia during a Cesarean section birth can later alter the development of stress-induced sensitization of dopamine transmission in the nucleus accumbens. Dams were decapitated on the last day of gestation and the entire uterus was removed by Cesarean section. Pups were then delivered either immediately (Cesarean section group) or were immersed in a 37 degrees C saline bath for 3.5 or 13.5 min (Cesarean section+anoxia groups) before delivery of the pups. A fourth group of pups that were born vaginally served as controls (Vaginal group). Three to four months postnatally, animals from each group were implanted with monoamine-selective carbon-fiber electrodes into the nucleus accumbens. Voltammetry was used to monitor the dopamine response to each of five consecutive, once daily, 15-min exposures to tail-pinch stress. The results show that the first exposure to stress elicited dopamine signal increases of comparable amplitudes and durations in all animals. However, when compared to the initial stress response, the fourth and fifth exposures to tail-pinch elicited significantly longer-lasting dopamine responses in animals born by Cesarean section, either with or without added anoxia. In contrast, there was no significant day-to-day enhancement of the stress response in control, vaginally born animals. The findings reported here provide experimental support for the idea that birth complications may contribute to the pathophysiology of psychiatric disorders, in particular those that involve central dopamine dysfunction, such as schizophrenia. Specifically, our results suggest that subtle alterations in birth procedure may be sufficient to increase the sensitivity of mesolimbic dopamine neurons to the effects of repeated stress in the adult animal.
动物研究的证据表明，胎儿经历一段时间的缺氧（这是许多分娩并发症常见的后果）会导致中脑腹侧多巴胺功能的长期改变。当动物反复受到应激时，这些多巴胺神经元，特别是那些支配伏隔核的神经元，也会出现长期的功能变化。在本研究中，我们探讨了剖宫产时的一段时间缺氧是否会在日后改变应激诱导的伏隔核多巴胺传递致敏的发展。在妊娠最后一天将母鼠断头，通过剖宫产取出整个子宫。然后在幼崽分娩前，将幼崽立即取出（剖宫产组），或将其浸入37摄氏度的盐水中3.5或13.5分钟（剖宫产+缺氧组）。第四组经阴道分娩的幼崽作为对照（阴道分娩组）。在出生后三到四个月，将每组动物的单胺选择性碳纤维电极植入伏隔核。使用伏安法监测多巴胺对连续五天、每天一次、每次15分钟的夹尾应激的反应。结果表明，首次暴露于应激时，所有动物的多巴胺信号增加幅度和持续时间相当。然而，与初始应激反应相比，在剖宫产出生的动物中，无论是否添加缺氧，第四次和第五次夹尾暴露引发的多巴胺反应持续时间明显更长。相比之下，经阴道分娩的对照动物的应激反应没有明显的逐日增强。此处报告的研究结果为出生并发症可能导致精神疾病的病理生理学，特别是那些涉及中枢多巴胺功能障碍的疾病（如精神分裂症）这一观点提供了实验支持。具体而言，我们的结果表明，出生过程中的细微改变可能足以增加成年动物中脑边缘多巴胺神经元对反复应激影响的敏感性。
