PRENATAL ALCOHOL--ENDOCRINE AND BEHAVIORAL EFFECTS

在上一次赠款期间获得的结果显示，一些长期的 胎儿酒精暴露(FAE)男性与对照组的比较 包括：1)成年后昼夜节律的改变，2) 大鼠床核内精氨酸加压素含量的降低 终纹(BNST)3)女性化的用水模式 18天前服用睾丸素可逆转成年期 妊娠19个月，4)视上核的解剖尺寸减小 5)增加了对雌激素刺激作用的行为敏感性 运动节律。我们的一些发现表明，老年人的衰老速度加快 雄性异种的生物钟。这项建议中的研究包括 旨在测试胎儿酒精暴露将加速这一假设 昼夜节律控制中与年龄相关的变化。 实验旨在验证这一衰老假说，使用两种方法 行为和荷尔蒙节律。其他研究将检验这一假设。 昼夜节律的变化对衰老或压力的反应将 与精氨酸加压素(AVP)和/或血管活性改变有关 肠肽(VIP)在视交叉上核的表达 将对FAE动物的酒精耐受性进行研究 FAE脑内AVP水平降低的功能意义。 我们还包括对有效剂量的睾丸素的研究，以 帮助对抗酒精在性别分化上的女性化 男性大脑。 最后，我们在这一批款期内取得的结果表明， 围产期睾酮(T)的抑制或减弱 孕期最后一周的酒精暴露不足以 显著改变成年雄性或雌性大鼠的性行为。 尽管这被认为是下丘脑神经发生和 在大鼠分化过程中，酒精暴露在这一时期不会 改变视前区的性二形核(SDN)的大小 无论男女。然而，接触酒精确实会导致显著的增加。 FAE雄性动物对雌激素诱导轮回的行为敏感性 跑步。这些结果表明，其他因素可能参与了 FAE动物性二态行为的长期变化 被我们自己和其他人观察到的。因此，我们建议将我们的重点放在 这方面的努力对FAE动物脑芳香酶活性的影响。总的来说， 这些研究旨在阐明长期的行为影响 胎儿期酒精对乙醇作用所致的昼夜节律的影响 围产期的性腺激素。

Results obtained during the last grant period reveal a number of long-term effects in fetal alcohol exposed (FAE) males compared to controls including: 1) alterations in circadian rhythms in adulthood, 2) decreases in arginine vasopressin (AVP) content in the bed nucleus of the stria terminalis (BNST) 3) a feminized water consumption pattern in adulthood which is reversed by prenatal testosterone treatment on days 18 and 19 of gestation, 4) decreased anatomical size of the supraoptic nucleus and 5) increased behavioral sensitivity to estrogen's stimulatory effect on locomotor rhythms. Several of our findings suggest an accelerated aging of the biological clock in the FAE male. Studies in this proposal are designed to test the hypothesis that fetal alcohol exposure will accelerate the age-related alterations in the control of circadian rhythms. Experiments are designed to test this aging hypothesis using both behavioral and hormonal rhythms. Other studies will test the hypothesis that alterations in circadian rhythms in response to aging or stress will be associated with changes in arginine vasopressin (AVP) and/or vasoactive intestinal peptide (VIP) expression in the suprachiasmatic nucleus. Studies of ethanol tolerance in FAE animals will be conducted to examine the functional significance of the reduced levels of AVP in the FAE brain. We have also included studies of an efficacious dose of testosterone to help counter the feminizing of ethanol on the sexual differentiation of the male brain. Finally, we have obtained results during this grant period indicating that the suppression or attenuation of the perinatal testosterone (T) surges by ethanol exposure during the last week of gestation is insufficient to significantly alter sex behavior of male or female rats in adulthood. Although this is recognized as the period of hypothalamic neurogenesis and differentiation in the rat, alcohol exposure during this period does not alter the size of the sexually dimorphic nucleus of the preoptic area (SDN) in either sex. Alcohol exposure does, however, produce a marked increase in the behavioral sensitivity of FAE males to estrogen-induced wheel running. These results suggest that additional factors may be involved in the long-term alterations in sexually dimorphic behaviors of FAE animals observed by ourselves and others. Therefore, we propose to focus our efforts in this area on brain aromatase activity in FAE animals. Overall, these studies are designed to elucidate the long-term behavioral effects of prenatal ethanol on circadian rhythms resulting from ethanol's actions on gonadal hormones during the perinatal period.