Social_affiliation_and_alcohol_drinking_in_rodents

描述(由申请人提供)：社会背景在酗酒和酗酒的发病和复发中起着重要的作用，但这方面的酗酒和酗酒还没有成功地在啮齿类动物身上模拟。最近，我们开发了利用草原田鼠(Microtus Ochrogaster)来研究对酒精消费的负面(促进)和积极(抑制)社会影响。具体地说，我们证明了这种物种对酒精的偏好和大量的酒精摄入量，并表明成对饲养的草原田鼠相互影响对方的饮酒。当田鼠被成双成对地引入酒精时，它们比被引入独舍时表现出更高的酒精偏好。在这些配对中，一只田鼠影响(即增加)其伴侣的酒精消费-建模促进了对饮酒的影响。相比之下，在高饮酒率和低饮酒率的田鼠配对过程中，先前在独居时经历过酒精的田鼠，基础摄入量较高的田鼠往往会减少饮酒量，从而与其伴侣匹配-建模抑制社会影响。因此，草原田鼠可以作为第一个啮齿动物模型，研究特定的人际关系对两个方向的高酒精饮酒的影响。我们假设，草原田鼠和人类一样，通过声音交流影响伴侣的饮酒率，这种影响受到支配/服从关系、阿片类药物和加压素(AVP)系统的调节。我们建议通过以下四个具体目标来检验这一假设。具体目标1：检验社会对饮酒的影响是否通过同步饮酒而发生，是否受到显性-顺从性交互作用的影响。具体目标2：测试紫外线是否有助于田鼠的协调饮酒，进一步提高我们模型的有效性。具体目标3：测试已建立的针对内源性阿片系统的酒精中毒药物疗法的疗效是否受到社会影响的影响。具体目标4：测试已知的调节草原田鼠社会联系的AVP系统是否有助于调节协调饮酒。综上所述，这项工作将首次揭示在啮齿动物模型中调节过度饮酒的社会影响的生物机制。 公共卫生相关性：社会背景在酗酒和酗酒的发病和复发中起着重要作用，但人们对酒精中毒的这一方面的机制知之甚少。在这项应用中，我们将使用草原田鼠作为啮齿动物模型来研究特定社会背景对过度饮酒的潜在影响的机制。这些研究的成功可能会为酒精中毒的治疗策略提供新的见解。

DESCRIPTION (provided by applicant): Social affiliations play an important role in the onset and relapse of alcoholism and heavy drinking, yet this aspect of alcoholism and alcohol abuse has not been successfully modeled in rodents. Recently we developed the use of prairie voles (Microtus ochrogaster) to study negative (facilitating) and positive (inhibitory) social influences on alcohol consumption. Specifically, we demonstrated alcohol preference and heavy ethanol intake in this species, and showed that pair-housed prairie voles influence each other's drinking. When voles are introduced to alcohol in pairs they exhibit higher alcohol preference than when they are introduced to alcohol being single-housed. In these pairs, one vole influences (i.e., increases) alcohol consumption of its partner - modeling facilitating influences on alcohol drinking. In contrast, during pairing of high- and low-drinking voles that have previously experienced alcohol when they were single- housed, the vole with higher basal intake tends to decrease its drinking thereby matching its partner - modeling inhibitory social influences. Thus, the prairie vole could serve as the first rodent model of the effects of specific inter-personal affiliations on high alcohol drinking in both directions. We hypothesize that prairie voles influence their partner's rate of alcohol consumption via acoustic communication as do humans and that this influence is regulated by dominant/submissive relations, the opiate and the vasopressin (AVP) systems. We propose to test this hypothesis through following four Specific Aims. Specific Aim 1: To test whether the social influences on alcohol drinking occur by synchronizing alcohol drinking and are influenced by dominant-submissive interactions. Specific Aim 2: To test the whether USVs contribute to coordinated drinking in voles further increasing the validity of our model. Specific Aim 3: To test whether the efficacy of an established pharmacotherapy of alcoholism targeting the endogenous opiate system is modulated by social influences. Specific Aim 4: To test whether the AVP system known to regulate social affiliations in prairie voles contributes to regulation of coordinated drinking. Taken together this work will for the first time reveal information on the biological mechanisms regulating social influence on excessive alcohol drinking in a rodent model. PUBLIC HEALTH RELEVANCE: Social affiliations play a substantial role in the onset and relapse of alcoholism and heavy drinking, yet the mechanisms of this aspect of alcoholism are poorly understood. In this application we will use the prairie vole as a rodent model to study the mechanisms underlying effects of specific social affiliations on excessive alcohol use. The success of these studies may provide new insights into strategies for therapeutic treatments of alcoholism.