Early Stress & Alcoholism: Neurobiological Analysis

酗酒和酗酒是我们社会的主要负担。虽然发展过度 饮酒模式受到许多因素的影响，一般的压力，特别是童年时期的压力， 被认为是这一过程中的重要病因因素。事实上，慢性压力已经被证明 改变与吸毒有关的许多大脑系统的神经传递，并改变 各种滥用药物，包括酒精。然而，我们对神经生物学反应 可能会改变受试者对酒精的反应 引人注目的是，许多大脑区域，包括眶和内侧前额叶皮层，杏仁核和 海马体也是大脑的一部分，它被证明可以调节对压力的反应。 奖赏回路，这是过度饮酒的核心。神经系统的这种共性 神经回路表明，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，中缝背核的含降钙素的神经元，它支配所有的神经元。 上面列出的区域，沿着下丘脑，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 儿童压力和乙醇的相互作用，采用一个充分研究的儿童压力模型， 恒河猴，托儿所饲养。通过比较幼儿园饲养的年轻成年猴子和正常母亲- 从同一群体饲养的对照，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，在童年时期经历过创伤性事件，如与父母分离， 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 未知拟议的研究旨在直接解决儿童压力的机制， 通过研究动物的饮酒行为、大脑结构和功能， 经历了母亲的分离。这个项目的信息可以对如何 受创伤的儿童可能受到保护，以后不会滥用药物。

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.