Druse M J, Tajuddin N, Kuo A, Connerty M
Department of Molecular and Cellular Biochemistry, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois 60153.
J Neurosci Res. 1990 Oct;27(2):233-40. doi: 10.1002/jnr.490270214.
Previous studies from this and other laboratories suggest that dopamine is decreased in selected brain regions of postnatal rats exposed to ethanol in utero. The present study expands previous work by examining the effects of in utero ethanol exposure on dopamine D1 and D2 binding sites and dopamine uptake in postnatal rats. In addition, dopamine content in the brain stem and frontal cortex of fetal and neonatal rats was examined. The experimental results indicate that in utero ethanol exposure markedly affects the postnatal development of the dopaminergic system in the striatum and frontal cortex. We observed a marked, transient deficiency of striatal dopamine (greater than 40% decrease at 19 days) and dopamine uptake sites (approximately 25% decrease in Vmax at 35 days). The Bmax for striatal dopamine D1 binding sites was decreased by greater than 20% at both 19 and 35 days. Cortical D1 sites were markedly decreased at 19 days (greater than 40%). In contrast, the number of striatal D2 receptors was unaffected by in utero ethanol exposure at both ages. Analysis of tissue from neonatal rats demonstrated a marked dopamine deficiency in ethanol-exposed rats on postnatal day 5. In light of the proposed morphogenic actions of dopamine early in development, it is possible that the early dopamine deficiency contributes to the abnormal postnatal development of the dopaminergic system.
来自本实验室及其他实验室的先前研究表明,子宫内接触乙醇的新生大鼠的特定脑区中多巴胺水平降低。本研究通过检测子宫内乙醇接触对新生大鼠多巴胺D1和D2结合位点以及多巴胺摄取的影响,扩展了先前的工作。此外,还检测了胎儿和新生大鼠脑干及额叶皮质中的多巴胺含量。实验结果表明,子宫内乙醇接触显著影响纹状体和额叶皮质中多巴胺能系统的产后发育。我们观察到纹状体多巴胺显著且短暂的缺乏(19天时减少超过40%)以及多巴胺摄取位点(35天时Vmax降低约25%)。纹状体多巴胺D1结合位点的Bmax在19天和35天时均降低超过20%。皮质D1位点在19天时显著降低(超过40%)。相比之下,两个年龄段的子宫内乙醇接触均未影响纹状体D2受体的数量。对新生大鼠组织的分析表明,乙醇暴露组大鼠在出生后第5天存在显著的多巴胺缺乏。鉴于多巴胺在发育早期具有拟态发生作用,早期多巴胺缺乏可能导致多巴胺能系统产后发育异常。