The Effect of Vicarious Exposure to Social Defeat on Alcohol Intake

项目摘要 酒精中毒和抑郁症的共病表现非常常见。因此，关键是 确定这些条件的神经生物学成分如何重叠，以促进我们对 共同的风险因素和机制，影响这种并发症。从这些信息中获得的信息 研究有助于促进可用于靶向特定的治疗方法的发展， 酒精中毒患者。最近，我们的小组描述了一种双向关系， 酒精暴露和抑郁样行为使用社会失败压力（SDS）范式，一个主要的 抑郁症的临床前模型在该模型中，雄性小鼠在身体上被更大的同种小鼠击败， 然后容纳在透明分隔器的另一侧。当长期暴露于这种应激源时，小鼠将 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， 小鼠攻击行为的性别差异。本建议的目的是建立一个模式， 我们的实验室，将使我们能够评估酒精寻求和抑郁症之间的关系， 在女性和男性受试者中的行为。为了实现这一目标，我们将利用最近开发的模型 实验对象观察到另一只动物的社交失败，称为替代性失败压力（VDS）。VDS 包括从一个与失败发生地相邻的隔间观察社交失败过程 地方最近发表的研究表明，该模型在男性和女性中产生了类似的抑郁样表型。 雌性老鼠在拟议的研究中，我们将使用VDS方案来研究 抑郁样行为和酒精消耗的雄性和雌性小鼠。此外，我们将确定，如果 长期酒精给药改变了对随后的VDS暴露的敏感性。这些研究将进一步 我们目前对男性和女性共病抑郁症和酗酒的机制的了解， 女性本研究结果将提供一个实验基础，可用于 未来的项目，评估这些进程的机制， 治疗目标

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.