Social_affiliation_and_alcohol_drinking_in_rodents

描述（由申请人提供）：社会关系在酒精中毒和大量饮酒的发作和复发中起着重要作用，然而酒精中毒和酒精滥用的这一方面还没有在啮齿动物中成功地建立模型。最近，我们利用草原田鼠（Microtus ochrogaster）来研究消极（促进）和积极（抑制）社会对酒精消费的影响。具体来说，我们证明了该物种对酒精的偏好和大量的乙醇摄入，并表明成对居住的草原田鼠会影响彼此的饮酒。当田鼠成对地接触酒精时，它们比单独接触酒精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）其伴侣的饮酒量——建模促进了对饮酒的影响。相比之下，在高饮酒量和低饮酒量田鼠的配对过程中，基础摄入量较高的田鼠倾向于减少饮酒量，从而匹配其伴侣-模拟抑制性社会影响。因此，草原田鼠可以作为第一个啮齿类动物模型，研究特定的人际关系对双向高酒精饮酒的影响。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量，这种影响受支配/服从关系、阿片类药物和抗利尿激素（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。具体目的1：检验社会对饮酒的影响是否通过同步饮酒发生，并受支配-服从互动的影响。具体目的2：测试usv是否有助于田鼠的协调饮酒，进一步提高我们的模型的有效性。特定目的3：测试针对内源性阿片系统的既定酒精中毒药物治疗的疗效是否受到社会影响的调节。具体目标4：测试已知调节草原田鼠社会关系的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学机制。

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.