NEUROHUMORAL AND PRENATAL DETERMINANTS OF ALCOHOL INTAKE

本项目的长期目标是了解 助长和/或倾向于酒精成瘾和方法， 这种机制会因产前接触酒精而改变。 使用 大鼠乙醇摄入和偏好模型， 在子宫内给予乙醇（17.5%或35%乙醇衍生的卡路里） (from妊娠第6天至第15天或第20天）将研究配对喂养 将包括轭动物以控制潜在的营养 方面的影响. 大鼠的乙醇摄入量和偏好将在三个 不同的产后年龄。 内源性性类固醇可能 调节产前乙醇暴露对产后乙醇的影响 摄入量将通过考虑胎儿位置的作用和 子宫与同性或异性兄弟姐妹的接近。 的影响 产前乙醇暴露对离散脑神经递质释放的影响 发育大鼠的区域将使用体内 微透析 多巴胺，去甲肾上腺素和血清素的释放将 在丘脑、纹状体和内侧前额叶皮层中测量， 清醒和自由活动的动物;将测量运动行为 同时，急性剂量的乙醇的影响也将 测定 最后，乙醇消费量与 和脑中神经递质的释放将被研究;在体内 微透析将与乙醇测量同时进行 摄入 一个重要的目标将是区分哪种神经化学物质 事件发生在乙醇摄入之前或引起乙醇摄入， 乙醇摄入的结果或后果;后续研究将 研究这些关系是如何被产前酒精暴露改变的。 本项目中提出的工作结果应阐明 酒精摄入量的决定因素，所涉及的机制，并通过这样做， 导致制定适当的干预措施， 预防和/或治疗酒精成瘾。

The long-term goal of this project is to understand the mechanisms subserving and/or predisposing to addiction to alcohol and the ways in which such mechanisms are altered by prenatal exposure to alcohol. Using a model of ethanol intake and preference in rats, the effects of administering ethanol (17.5% or 35% ethanol derived calories) in utero (from Day 6 to Day 15 or 20 of gestation) will be investigated pair-fed yoked animals will be included to control for potential nutritional effects. Ethanol intake and preference of rats will be determined at three different postnatal ages. The possibility that endogenous sex steroids may modulate the effects of prenatal ethanol exposure on postnatal ethanol intake will be examined by considering the role of fetal position and in utero contiguity to siblings of the same or opposite sex. The effects of prenatal ethanol exposure on neurotransmitter release in discrete brain regions of developing rats will be determined with the use of in vivo microdialysis. Dopamine, norepinephrine and serotonin release will be measured in nucleus accumbens, striatum and medial prefrontal cortex of awake and freely moving animals; motor behavior will be measured concomitantly and the effects of acute doses of ethanol will also be determined. Lastly, the temporal relationship between ethanol consumption and neurotransmitter release in brain will be studied; in vivo microdialysis will be conducted concurrently with measurement of ethanol intake. An important goal will be to distinguish which neurochemical events precede or elicit ethanol intake and which neurochemical events are the result or consequence of ethanol intake; subsequent studies will examine how these relationships are altered by prenatal ethanol exposure. The results of the work proposed in this project should elucidate the determinants of alcohol intake, the mechanisms involved, and by doing so,, lead to the development of appropriate interventions that could be used to prevent and/or treat alcohol addiction.