Tajuddin N, Druse M J
Department of Biochemistry and Biophysics, Loyola University Stritch School of Medicine, Maywood, IL 60153.
Alcohol. 1988 Nov-Dec;5(6):465-70. doi: 10.1016/0741-8329(88)90084-5.
This laboratory previously demonstrated that chronic maternal ethanol consumption results in a marked deficiency of cortical serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) and of 5-HT uptake sites in the 19- and 35-day-old offspring. In order to determine whether in utero exposure to ethanol similarly affects other components of the serotonergic system we examined the influence of chronic maternal ethanol consumption on cortical, serotonergic 5-HT1 binding sites in developing offspring. Female Sprague-Dawley rats were pair-fed, using control or 6.6% (v/v) ethanol liquid diets on a chronic basis prior to parturition. Serotonergic 5-HT1 sites were measured in synaptosomal membranes from whole cortex and cortical regions from developing offspring. Serotonergic 5-HT1 sites were assessed by measuring the binding of [3H]-5-HT to synaptosomal membranes in the presence and absence of nonradioactive 5-HT. Serotonergic 5-HT2 sites were blocked by including 100 nM spiperone in the assay buffer. The results demonstrated that the 19- and 37-day-old offspring of ethanol-fed rats had a significant (approximately 10-40%) reduction in the Bmax for serotonergic 5-HT1 binding sites on synaptosomal membranes from whole cortex (p less than 0.025), motor cortex (p less than 0.01), and somatosensory cortex (p less than 0.025). However, the binding affinity (Kd) for serotonin was not significantly altered (p greater than 0.05). These results emphasize the sensitivity of the developing cortical serotonergic system to prenatal ethanol exposure.
本实验室先前已证明,孕期长期摄入乙醇会导致19日龄和35日龄子代的皮质血清素(5-羟色胺,5-HT)、5-羟吲哚乙酸(5-HIAA)以及5-HT摄取位点显著缺乏。为了确定子宫内乙醇暴露是否同样会影响血清素能系统的其他成分,我们研究了孕期长期摄入乙醇对发育中后代皮质血清素能5-HT1结合位点的影响。在分娩前,将雌性Sprague-Dawley大鼠成对饲养,分别给予对照或6.6%(v/v)乙醇液体饲料。测定发育中后代整个皮质和皮质区域突触体膜中的血清素能5-HT1位点。通过测量[3H]-5-HT在有无非放射性5-HT存在时与突触体膜的结合来评估血清素能5-HT1位点。在测定缓冲液中加入100 nM螺哌隆可阻断血清素能5-HT2位点。结果表明,乙醇喂养大鼠的19日龄和37日龄子代,其整个皮质(p<0.025)、运动皮质(p<0.01)和躯体感觉皮质(p<0.025)突触体膜上血清素能5-HT1结合位点的最大结合容量(Bmax)显著降低(约10 - 40%)。然而,5-羟色胺的结合亲和力(Kd)没有显著改变(p>0.05)。这些结果强调了发育中的皮质血清素能系统对产前乙醇暴露的敏感性。