Prenatal stress in rats : effects of cytogenesis, cocaine-induced place preference and dopamine

本研究探讨了产前应激对脑室下区细胞发生的影响，这可能与奖励可卡因在子代大鼠中的有效性改变有关。在胚胎的5天（E13至E17），怀孕的母鼠被限制在Bolman笼中，每天3次，每次45分钟，暴露于两个明亮的（150 W）灯。对于细胞增殖研究，向母鼠注射细胞增殖标记物5-溴-2 '脱氧尿苷（BrdU ; 50 mg/kg，i. p.），在E13、E15和E17天的每次压力会话之后。幼仔，然后灌注出生后第7天或第10天和BrdU阳性细胞计数的颗粒下区的的肌和脑室下区，分别。为探讨可卡因对子代大鼠的奖赏效应，对10周龄的子代大鼠分别腹腔注射可卡因（0、2.5、5.0、10.0 mg/kg）进行训练。建立位置偏好。此外，用在体微透析和高效液相色谱法研究了可卡因对仔鼠丘脑外侧核多巴胺含量的影响，结果表明：（1）产前应激组仔鼠丘脑颗粒下区和脑室下区的BrdU阳性细胞数均显著减少;（2）条件位置偏爱试验显示可卡因的奖赏效应高于对照组。但是，产前应激并不影响可卡因增加的细胞外多巴胺在nucleus bens.The结果表明，产前应激，特别是施加在怀孕后期，可能会导致减少细胞增殖的室管膜下区在胎儿和一个hypersensitivity奖励可卡因。后来的改变似乎不是由于多巴胺对可卡因的过度反应。

The present study examined the effects of prenatal stress on the cytogenesis in the subventricular zone that may implicate in the altered effectiveness of rewarding cocaine in the offspring rats.During five embryonic days (E13 to E17), pregnant dams were restrained for 45 min, three times a day, in the Bolman cages exposed to two bright (150w) lights. For cell-proliferation study, dams were injected with a cell-proliferation marker 5-bromo-2' deoxyuridine (BrdU ; 50mg/kg, i.p.), following each stress session on days of E13, E15, and E17. Pups were then perfused on postnatal day 7 or 10 and BrdU-positive cells were counted in the subgranular zone of the hippocamus and the subventricular zone, respectively. To investigate rewarding effectiveness of cocaine in the offspring rats, ten-week-old offsprings were trained with cocaine (0, 2.5, 5.0, 10.0 mg/kg, i.p.) to establish place preference. Additionally, cocaine-enhanced extracellular dopamine concentration in the nucleus accumbens, was examined by using in-vivo microdialysis and high-performance liquid chromatography.The prenatally stressed offsprings showed (1) remarkably fewer BrdU positive cells not only in the subgranular zone but also in the subventricular zone and (2) Higher rewarding effectiveness of cocaine revealed in conditioned place preference test than that in control offsprings. But, prenatal stress did not affect the cocaine-increased extracellular dopamine in the nucleus accumbens.The results indicate that prenatal stress, particularly applied during the later period of pregnancy, may lead to a reduction in cell proliferation of the subventricular zone in the fetus and a hypersensitization to the rewarding cocaine. The later alteration seems not due to the hyperreaction of accumbal dopamine to the cocaine.