Perinatal distress leads to lateralized medial prefrontal cortical dopamine hypofunction in adult rats
Perinatal distress leads to lateralized medial prefrontal cortical dopamine hypofunction in adult rats
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DOI：
10.1523/jneurosci.20-14-05538.2000
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发表时间：
2000-07-15
影响因子：
5.3
通讯作者：
Gratton, A
中科院分区：
文献类型：
--
作者：
Brake, WG;Sullivan, RM;Gratton, A
产科并发症涉及缺氧或长期缺氧被怀疑会增加精神分裂症和注意力缺陷多动障碍等精神障碍的风险。在以前的研究中，我们报道了在剖腹产（C）分娩期间宫内缺氧的成年大鼠中增强的丘脑核（NAcc）多巴胺（DA）功能的证据。在本研究中，我们使用伏安法和单胺敏感电极来调查的可能性，这种功能亢进的meso-NAcc系统是由于内侧前额叶皮层（PFC）的抑制控制的损失。我们监测了DA反应，重复每日一次的压力，在右侧或左侧PFC的成年雄性大鼠阴道出生（VAG）或剖腹产，无论是（C + 15）或没有（C + 0）的额外15分钟的宫内缺氧。在C + 15动物，我们观察到一个明显的和持久的钝化的压力诱导的DA释放在右侧PFC，但不是在左侧;重复测试，一个类似的模式，阻尼右侧PFC DA压力反应出现在C + 0动物。此外，C + 15动物自发性比VAG和C + 0动物更活跃，并显示PFC DA转运蛋白密度增加，也偏向右半球。然而，没有证据表明PFC D-1和D-2受体水平在出生组或半球之间存在差异。这些研究结果表明，围产期并发症涉及缺氧可能有助于精神障碍的病因，已被链接到中央DA传输和偏侧PFC功能障碍的障碍的机制。
Obstetric complications involving anoxia or prolonged hypoxia are suspected to increase the risk for such mental disorders as schizophrenia and attention deficit-hyperactivity disorder. In previous studies, we reported evidence of enhanced nucleus accumbens (NAcc) dopamine (DA) function in adult rats subjected to intrauterine anoxia during cesarean (C) section birth. In the present study, we used voltammetry and monoamine-sensitive electrodes to investigate the possibility that this functional hyperactivity of the meso-NAcc system is attributable to a loss of inhibitory control from the medial prefrontal cortex (PFC). We monitored the DA responses to repeated once-daily stress in the right or left PFC of adult male rats born vaginally (VAG) or by C-section, either with (C + 15) or without (C + 0) an additional 15 min of intrauterine anoxia. In C + 15 animals, we observed a pronounced and persistent blunting of stress-induced DA release in the right PFC but not in the left; with repeated testing, a similar pattern of dampened right PFC DA stress responses emerged in C + 0 animals. In addition, C + 15 animals were spontaneously more active than VAG and C + 0 animals and displayed an increase in PFC DA transporter density that was also lateralized to the right hemisphere. There was no evidence, however, that PFC D-1 and D-2 receptor levels differed between birth groups or hemisphere. These findings suggest a mechanism by which perinatal complications involving anoxia might contribute to the etiology of mental disorders that have been linked to disturbances in central DA transmission and lateralized PFC dysfunction.