Lucchi L, Covelli V, Petkov V V, Spano P F, Trabucchi M
Pharmacol Biochem Behav. 1983 Oct;19(4):567-70. doi: 10.1016/0091-3057(83)90328-3.
The fetal alcohol syndrome is characterized by a number of abnormalities consisting of a pre- and post-natal growth deficiency, microcephaly, areas of abnormal nerve cell migration in the brain, mental and psychomotor retardation in children of alcoholic women. These findings may be referred as a teratogenic effect of ethanol on the central nervous system. In order to investigate the above ethanol-neurotoxic effect the striatal dopaminergic transmission was studied. The dopaminergic turnover was measured by 3,4-dihyroxyphenilacetic acid content and 3H-Spiperone binding has been carried out to determine dopaminergic receptor alterations induced by chronic ethanol consumption during pregnancy. Our work demonstrates long-lasting modifications of dopaminergic neuronal function after exposure of the experimental animal to ethanol during fetal life. In particular, a decreased receptor function has been observed in rats exposed to ethanol only during the perinatal period. In the same group of rats, diminished receptor activity leads to an enhancement in DOPAC content still detectable after a long period from cessation of ethanol treatment. Neurochemical data are reinforced by behavioral observations. In fact, a significant decrease of spontaneous locomotor activity in the rats chronically treated with ethanol during fetal life was observed. In addition, the altered response of locomotor activity after drug administration may be ascribed to the modified dopaminergic function. With this experimental approach we assume that the action of ethanol on the central nervous system may be a marker of its teratogenic effect.
胎儿酒精综合征的特征是一系列异常,包括产前和产后生长发育迟缓、小头畸形、大脑中神经细胞迁移异常区域、酗酒女性的子女出现智力和精神运动发育迟缓。这些发现可被认为是乙醇对中枢神经系统的致畸作用。为了研究上述乙醇神经毒性作用,对纹状体多巴胺能传递进行了研究。通过测定3,4 - 二羟基苯乙酸含量来测量多巴胺能周转率,并进行了3H - 司哌罗宁结合实验,以确定孕期长期摄入乙醇所诱导的多巴胺能受体改变。我们的研究表明,实验动物在胎儿期接触乙醇后,多巴胺能神经元功能会发生长期改变。特别是,仅在围产期接触乙醇的大鼠中观察到受体功能下降。在同一组大鼠中,受体活性降低导致DOPAC含量增加,在停止乙醇处理很长一段时间后仍可检测到。行为观察结果进一步证实了神经化学数据。事实上,观察到在胎儿期长期接受乙醇处理的大鼠自发运动活动显著减少。此外,给药后运动活动反应的改变可能归因于多巴胺能功能的改变。通过这种实验方法,我们认为乙醇对中枢神经系统的作用可能是其致畸作用的一个标志。