Early Stress & Alcoholism: Neurobiological Analysis

酗酒和酗酒是我们社会的主要负担。而过度的发展 饮酒模式受到许多因素的影响，一般情况下，压力，特别是童年时期的压力， 被认为是这一过程中的重要病因。事实上，长期的压力已经被证明是 改变许多与吸毒有关的大脑系统中的神经传递，并改变 各种滥用药物，包括酒精。然而，关于神经生物学反应如何，人们知之甚少。 压力可能会改变受试者对酒精的反应方式。 令人惊讶的是，许多大脑区域，包括眼眶和内侧前额叶皮质，杏仁核和 海马体也是大脑的一部分，海马体已被证明可以调节对压力的反应 奖赏回路，这是过度饮酒发展的核心。神经的这种共性 电路表明，这些区域可能在调节压力对酒精的影响方面发挥作用。 消费。此外，中缝背核中含有5-羟色胺的神经元，它支配着 上面列出的区域以及下丘脑是应激反应的关键调节器，并且能够 来改变对药物的反应。该项目于2003年首次获得资助，旨在继续研究 儿童压力和酒精的相互作用通过使用一个研究良好的儿童压力模型 恒河猴，苗圃饲养。通过比较幼年托儿所饲养的猴子和正常母亲- 在同一群体中饲养的对照组，我们正在研究：1)饮酒行为，2)神经内分泌状态，3) 5-羟色胺转运体和受体，以及促肾上腺皮质激素释放因子受体。 与公共卫生的相关性：成年人，他们在童年经历过创伤事件，如与 他们的父母酗酒和酗酒的风险增加。这种风险增加的原因是 未知。这项拟议的研究旨在直接解决儿童压力的机制 通过研究饮酒行为以及动物的大脑结构和功能来导致成年酒精中毒 经历了母性分离。来自该项目的信息可以对以下方面产生重要影响 受到创伤的儿童可能会得到保护，不会在以后滥用药物。

Alcohol abuse and alcoholism are major burdens for our society. While the development of excessive drinking patterns is influenced by many factors, stress in general, and stress during childhood in particular, are believed to be important etiological elements in this process. Indeed, chronic stress has been shown to alter neurotransmission in many brain systems linked to drug taking and alter the rewarding properties of a variety of abused drugs, including alcohol. Little is known, however about how the neurobiological response to stress might alter the way a subject responds to alcohol. Strikingly, many of the brain regions, including the orbital and medial prefrontal cortex, the amygdala and the hippocampus, that have been shown to modulate the response to stress, are also part of the brain reward circuitry, which is central in the development of excessive drinking. This commonality of neural circuitry suggests that these regions may play a role in mediating the effects of stress on alcohol consumption. In addition, serotonin-containing neurons of the dorsal raphe nucleus, which innervates all of the areas listed above, along with the hypothalamus, is a key modulator of the stress response, and is able to modify the response to drugs as well. This project, first funded in 2003, is designed to continue to study the interaction of childhood stress and ethanol by employing a well-studied model of childhood stress in rhesus monkeys, nursery-rearing. By comparing young adult nursery-reared monkeys to normal mother- reared controls from the same colony, we are studying: 1) drinking behavior, 2) neuroendocrine status, 3) the serotonin transporter and receptors, and Corticotropin releasing factor receptors. Relevance to Public Health: Adults, who in childhood experience traumatic events like separation from their parents, are at increased risk for alcohol abuse and alcoholism. The causes for this increased risk are unknown. The proposed studies are designed to directly address the mechanisms by which childhood stress leads to adult alcoholism by studying the drinking behavior and brain structure and function of animals that experienced maternal separation. This information from this project can have important influences on how traumatized children may be protected from later substance abuse.