El-Khodor B F, Boksa P
Department of Psychiatry, McGill University, Douglas Hospital Research Center, Verdun, Quebec, Canada.
Neuroscience. 1998 Dec;87(4):893-904. doi: 10.1016/s0306-4522(98)00194-8.
We have previously reported that an apparently uncomplicated Caesarean section birth produces long-term alterations in steady-state levels of dopamine in the central nervous system of the rat. In addition, adult rats that had been born by Caesarean section, either with or without acute global anoxia, showed markedly greater dopamine release from the nucleus accumbens in response to repeated stress, in comparison to vaginally born controls. The aim of the present study was to test whether these birth complications also result in long-term changes in behavior mediated by dopamine systems. For this, we investigated effects of a low dose (0.5 mg/kg) of amphetamine on activity levels in three-month-old rats that had been born vaginally (control), by rapid Caesarean section, or by Caesarean section with 15 min of global anoxia. Amphetamine induced a significantly greater increase in locomotor activity in animals born by Caesarean section or by Caesarean section+ 15 min anoxia, in comparison to the drug's effects in vaginally born controls. Behavioral responses were further analysed from video recordings of the animals' behavior. In confirmation of automated activity counts, both animals born by Caesarean section and by Caesarean section + 15 min anoxia showed a significant increase in the duration and frequency of moving and a decrease in the duration and frequency of standing, in comparison to vaginally born controls. Animals delivered by Caesarean section showed a significant increase in the duration of sniffing and a decrease in the duration and frequency of grooming when compared to vaginally born controls. Animals delivered by Caesarean section + 15 min anoxia showed a significant increase in the duration and frequency of rearing, in comparison to controls. The pattern of behavioral changes observed indicates that, as adults, animals born by Caesarean section and by Caesarean section with added global anoxia both show heightened behavioral responses to amphetamine, in comparison to vaginally born animals. These findings highlight the sensitivity of dopamine pathways to variations in birth procedure and add experimental support to epidemiological evidence implicating birth complications in the pathophysiology of disorders involving central dopaminergic neurons, such as schizophrenia.
我们之前曾报道，表面上看似简单的剖宫产分娩会使大鼠中枢神经系统中多巴胺的稳态水平发生长期改变。此外，与经阴道分娩的对照大鼠相比，无论有无急性全身性缺氧，通过剖宫产出生的成年大鼠在反复应激时伏隔核释放的多巴胺明显更多。本研究的目的是测试这些分娩并发症是否也会导致由多巴胺系统介导的行为发生长期变化。为此，我们研究了低剂量（0.5毫克/千克）苯丙胺对三个月大经阴道分娩（对照）、快速剖宫产或剖宫产加15分钟全身性缺氧出生的大鼠活动水平的影响。与经阴道分娩的对照大鼠相比，苯丙胺对剖宫产或剖宫产加15分钟缺氧出生的动物的运动活动诱导出显著更大的增加。通过动物行为的视频记录进一步分析行为反应。与自动活动计数结果一致，与经阴道分娩的对照大鼠相比，剖宫产和剖宫产加15分钟缺氧出生的动物在移动的持续时间和频率上均显著增加，而站立的持续时间和频率则减少。与经阴道分娩的对照大鼠相比，剖宫产出生的动物嗅闻持续时间显著增加，梳理毛发的持续时间和频率减少。与对照相比，剖宫产加15分钟缺氧出生的动物竖立时的持续时间和频率显著增加。观察到的行为变化模式表明，作为成年动物，剖宫产和剖宫产加全身性缺氧出生的动物与经阴道出生的动物相比，对苯丙胺的行为反应均增强。这些发现突出了多巴胺通路对分娩过程变化的敏感性，并为流行病学证据提供了实验支持，这些证据表明分娩并发症与涉及中枢多巴胺能神经元的疾病（如精神分裂症）的病理生理学有关。
