NEUROHUMORAL AND PRENATAL DETERMINANTS OF ALCOHOL INTAKE

这个项目的长期目标是了解这些机制 对酒精上瘾的从属和/或诱因及其治疗方法 这些机制会因出生前接触酒精而改变。使用 大鼠酒精摄取和偏爱模型的建立及白藜芦醇的影响 宫内注射乙醇(17.5%或35%酒精卡路里) (从怀孕第6天到第15天或第20天)将进行配对喂养 有轭的动物将被纳入控制潜在的营养 效果。大鼠的酒精摄入量和偏好将在三点确定。 不同的出生后年龄。内源性类固醇可能会 调节产前酒精暴露对产后酒精的影响 摄入量将通过考虑胎位和胎位的作用进行检查 同性别或异性兄弟姐妹的子宫毗邻。的影响 产前酒精暴露对离散脑内神经递质释放的影响 发育中的大鼠的区域将通过使用体内的 微透析。多巴胺、去甲肾上腺素和5-羟色胺的释放 伏隔核、纹状体和内侧前额叶皮质的测量 清醒和自由活动的动物；运动行为将被测量 随之而来的是急性剂量乙醇的影响也将是 下定决心。最后，乙醇消费之间的时间关系 并将研究大脑中神经递质的释放；在体内 微渗析将与乙醇的测量同时进行 入口处。一个重要的目标将是区分哪些神经化学物质 酒精摄入之前或引发的事件以及哪些神经化学事件 酒精摄入的结果或后果；后续研究将 研究这些关系是如何通过产前酒精暴露而改变的。 这个项目中提出的工作结果应该说明 酒精摄入量的决定因素，涉及的机制，通过这样做， 导致制定适当的干预措施，可用于 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.