The Effect of Vicarious Exposure to Social Defeat on Alcohol Intake

项目总结 酗酒和抑郁的共同表现是非常普遍的。因此，至关重要的是 确定这些情况的神经生物学成分如何重叠，以促进我们对 影响这种共病的常见危险因素和机制。从这些信息中得出的信息 调查有助于开发可用于针对特定目标的治疗学 酗酒患者的群体。最近，我们小组描述了一种双向关系，即 使用社会失败压力(SDS)范式的酒精暴露和抑郁样行为，这是一个主要的 抑郁症的临床前模型。在这个模型中，雄性小鼠在身体上被一个更大的同种和 然后安放在透明隔板的另一边。当长期暴露在这种应激源中时，小鼠会 表现出被认为是抑郁样行为的行为表型，包括快感缺乏 和社交退缩。SDS模型的一个缺点是它只在男性受试者中有效，因为 小鼠攻击行为的性别差异。目前提案的目标是在以下方面建立一个模式 我们的实验室将使我们能够评估酗酒和抑郁样症状之间的关系 女性和男性受试者的行为。为了实现这一目标，我们将利用最近开发的模型 一个测试对象观察到另一种动物的社会失败，称为替代失败压力(VDS)。VDS 包括从失败处附近的隔间观察社交失败期 地点。最近发表的研究表明，这种模型在男性和女性中都会产生类似抑郁的表型。 雌性老鼠。在拟议的研究中，我们将使用VDS协议来调查 雄性和雌性小鼠的抑郁样行为和饮酒。此外，我们将确定是否 长期饮酒改变了对随后VDS暴露的敏感性。这些研究将取得进展 我们目前对男性和男性共患抑郁症和酗酒的潜在机制的了解 女性。从该方案中获得的结果将提供一个实验基础，可用于 未来的项目，评估这些进程背后的机制，并确定有希望的 治疗靶点。

PROJECT SUMMARY Comorbid expression of alcoholism and depression is extremely common. Thus, it is critical to determine how the neurobiological components of these conditions overlap to advance our understanding of the common risk factors and mechanisms that influence this comorbidity. The information derived from these investigations helps to contribute to the development of therapeutics that can be used to target specific populations of alcoholic patients. Recently, our group has described a bidirectional relationship between alcohol exposure and depression-like behavior using the social defeat stress (SDS) paradigm, a major preclinical model of depression. In this model, male mice are physically defeated by a larger conspecific and then housed on the other side of a transparent divider. When exposed chronically to this stressor, mice will exhibit behavioral phenotypes that are thought to be indicative of depressive-like behavior, including anhedonia and social withdrawal. One drawback of the SDS model is that it only works effectively in male subjects due to sex differences in aggressive behavior in mice. The objective of the current proposal is to establish a model in our laboratory that will allow us to assess the relationship between alcohol seeking and depressive-like behavior in both female and male subjects. To achieve this objective, we will utilize a recently developed model where a test subject observes the social defeat of another animal, called vicarious defeat stress (VDS). VDS involves observation of social defeat sessions from a compartment neighboring where the defeat is taking place. It was recently published that this model produces similar depressive-like phenotypes in both male and female mice. In the proposed studies, we will use the VDS protocol to investigate the relationship between depression-like behavior and alcohol consumption in male and female mice. Furthermore, we will determine if chronic alcohol administration alters the sensitivity to subsequent VDS exposure. These studies will advance our current knowledge of the mechanisms underlying comorbid depression and alcoholism in both males and females. The results obtained from this proposal will provide an experimental foundation that can be used for future projects assessing the mechanisms underlying these processes and for the identification of promising therapeutic targets.