Boksa Patricia, Zhang Ying
Department of Psychiatry, Douglas Mental Health University Institute, McGill University, 6875 LaSalle Boulevard, Montreal, Quebec H4H 1R3, Canada.
Psychopharmacology (Berl). 2008 Oct;200(3):381-91. doi: 10.1007/s00213-008-1213-9. Epub 2008 Jun 11.
Obstetric complications involving birth hypoxia are implicated in the etiology of disorders with dopaminergic dysfunction, such as schizophrenia. Cesarean section (C-section) birth in both humans and rats is associated with increased mild respiratory distress and with reduced levels of circulating catecholamines at birth, which normally serve to prime the lungs and activate other processes promoting extrauterine adaptation. Using a rat model, it has been found that C-section birth can produce long-term changes in central nervous system (CNS) dopamine function, compared to vaginal birth.
The present experiments tested if administering exogenous epinephrine at birth could reverse long-term changes in dopaminergic parameters in C-sectioned rats.
In the absence of stress at adulthood, no differences were observed between C-sectioned and vaginally born rats in levels of in vivo tyrosine hydroxylase (TH) activity and dopamine transporter (DAT) binding. However, after repeated mild stress at adulthood, C-sectioned rats showed increased TH activity in nucleus accumbens and increased DAT in dorsal striatum and accumbens, compared to vaginally born controls. A single injection of epinephrine to C-sectioned rats just after birth prevented the increased TH activity and DAT binding seen in C-sectioned rats after repeated mild stress at adulthood. There was also a trend for epinephrine at birth to partially reverse an increase in amphetamine-induced locomotion seen in C-sectioned rats at adulthood.
These results suggest that variations in levels of circulating catecholamines in the neonate at the time of birth could contribute to subtle long-term changes in CNS function.
涉及出生时缺氧的产科并发症与多巴胺能功能障碍性疾病(如精神分裂症)的病因有关。人类和大鼠的剖宫产出生都与出生时轻度呼吸窘迫增加以及循环儿茶酚胺水平降低有关,而循环儿茶酚胺通常用于启动肺部并激活其他促进宫外适应的过程。使用大鼠模型发现,与阴道分娩相比,剖宫产出生可导致中枢神经系统(CNS)多巴胺功能发生长期变化。
本实验测试了出生时给予外源性肾上腺素是否能逆转剖宫产大鼠多巴胺能参数的长期变化。
在成年期无应激情况下,剖宫产大鼠和经阴道分娩的大鼠在体内酪氨酸羟化酶(TH)活性水平和多巴胺转运体(DAT)结合方面未观察到差异。然而,成年期反复轻度应激后,与经阴道分娩的对照大鼠相比,剖宫产大鼠伏隔核中的TH活性增加,背侧纹状体和伏隔核中的DAT增加。在出生后立即给剖宫产大鼠单次注射肾上腺素,可预防成年期反复轻度应激后剖宫产大鼠出现的TH活性增加和DAT结合增加。出生时给予肾上腺素也有部分逆转成年期剖宫产大鼠中安非他明诱导的运动增加的趋势。
这些结果表明,出生时新生儿循环儿茶酚胺水平的变化可能导致中枢神经系统功能的细微长期变化。