PRENATAL CORTICOSTERONE INCREASES SPONTANEOUS AND D-AMPHETAMINE INDUCED LOCOMOTOR-ACTIVITY AND BRAIN DOPAMINE METABOLISM IN PREPUBERTAL MALE AND FEMALE RATS
PRENATAL CORTICOSTERONE INCREASES SPONTANEOUS AND D-AMPHETAMINE INDUCED LOCOMOTOR-ACTIVITY AND BRAIN DOPAMINE METABOLISM IN PREPUBERTAL MALE AND FEMALE RATS
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DOI：
10.1016/0306-4522(94)00605-5
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发表时间：
1995-05-01
期刊：
影响因子：
3.3
通讯作者：
FUXE, K
中科院分区：
文献类型：
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作者：
DIAZ, R;OGREN, SO;FUXE, K
近年来，糖皮质激素受体免疫反应和糖皮质激素受体信使RNA的表达均在多个脑区被发现，尤其是在大鼠脑发育后期的神经上皮细胞中。为了更好地了解应激通过释放母体肾上腺皮质类固醇对胎儿大脑发育的潜在影响，我们研究了孕鼠给予皮质酮对其青春期前后代运动活动的影响。在怀孕第16天，雌性大鼠植入安慰剂或皮质酮微丸(每天释放2.4 mg，连续7天)。出生后，它们的后代由养母哺育，以避免皮质酮颗粒对出生后的任何影响。在三周大的时候，对后代进行了自发运动行为测试。与安慰剂组相比，接受皮质酮治疗的母亲的男性和女性后代的自发行走、活动和养育能力都显著增加。在安慰剂组的雄性和雌性后代之间，没有发现显著的性别差异。在给予选择性多巴胺释放剂D-苯丙胺(1.5 mg/kg)后，我们观察到皮质酮处理的雄性子代行走、活动和养育活动显著增加。在雌性后代中，只有在d-苯丙胺治疗后，产前皮质酮治疗组的饲养活动显著高于安慰剂治疗组。经皮质酮处理的雄鼠和雌鼠的背侧纹状体和腹侧纹状体的基础多巴胺代谢(二羟基苯乙酸/多巴胺比值)增加。在雄性后代中，皮质酮治疗与右侧背侧纹状体多巴胺代谢优势的消失有关。这些结果表明，产前给予低生理剂量的皮质酮可以影响出生后自发运动活动和多巴胺功能的发育，这种影响方式在性别上有所不同。观察到的效果可能是通过直接激活胎儿大脑中的皮质酮受体来实现的。
Recently, both glucocorticoid receptor immunoreactivity and glucocorticoid receptor messenger RNA levels were found in multiple brain areas, especially in the neuroepithelium during the late prenatal development of the rat brain. To better understand the potential influence of stress on fetal brain development by release of maternal adrenocortical steroids, we have investigated the effects of corticosterone administration to pregnant rats on the locomotor activity of their prepubertal offspring. On day 16 of pregnancy female rats were implanted with either placebo or corticosterone pellets (release of 2.4 mg/day for seven days). After birth their offspring were nursed by foster mothers to avoid any postnatal effects of the corticosterone pellets. At three weeks of age, the offspring were tested for spontaneous motor behaviours. Both male and female offspring from corticosterone treated mothers showed significantly increased spontaneous ambulation, motility and rearing compared to placebo treated groups. No significant sex differences were found in locomotor activity between male and female offspring from placebo groups. Following d-amphetamine (1.5 mg/kg) treatment, a preferential dopamine releasing agent, we observed a significant increase in ambulation, motility and rearing activity in the male offspring treated with corticosterone. In the female offspring, only the rearing activity was significantly higher after d-amphetamine treatment in the prenatal corticosterone group compared with the placebo treated group. Basal dopamine metabolism (dihydroxyphenylacetic acid/dopamine ratio) was increased in the dorsal striatum and ventral striatum of male and female offspring from corticosterone-treated dams. In the male offspring, corticosterone treatment was associated with a disappearance of the right side dominance of dopamine metabolism in the dorsal striatum.These results suggest that prenatal administration of corticosterone in low physiological doses can affect the postnatal development of spontaneous locomotor activity and dopamine function in a manner which is partly different in the two sexes. The effects observed may be mediated by direct activation of corticosterone receptors in the fetal brain.