Ethanol-induced conditioned partner preference in mice

描述(由申请人提供)：饮酒行为和社会背景密切相关，特别是在年轻人中。同伴关系可以促进饮酒。同时，饮酒还能促进社会联系，就像流行的“饮酒伙伴”概念一样。归根结底，为了打击不健康的社交饮酒模式，重要的是要了解乙醇是如何塑造附属行为的神经化学的。我们已经建立了一个条件性伴偏好的小鼠模型，并且我们已经获得了初步的数据来证明乙醇(Etoh)诱导的雌性小鼠的社会偏好。条件性伴侣偏好类似于条件性位置偏好，但它包含了方法、认可度和从属关系的社会方面。这与人类的饮酒行为有关。到目前为止，在我们的初步研究中，雌性小鼠更喜欢以前喝醉过的同种动物。乙醇和雌二醇还有进一步的相互作用来促进社会偏好，因为在接受雌激素治疗的去卵巢女性(OVX E)中，EtoH诱导的伴侣偏好比没有雌激素的去卵巢女性(OVX E)更强。拟议的研究将使用C57BL/6雌性小鼠来扩展我们最初的观察。目的1a将确定在使用黄体酮的去势、去势和去势雌体中促进条件性伴侣偏爱的乙醇剂量范围。目的1b将通过测试有无睾丸素的切除睾丸的男性来检验乙醇诱导的条件性伴侣偏爱的性别差异。目标2将扩展条件伴侣偏好模型，以测试其他滥用药物(苯丙胺、吗啡)对社会纽带的影响。最后，目标3将开始探索乙醇诱导的条件性伴侣偏好的潜在机制。在这一点上，配对结合和附属行为对通过加压素V1a受体介导的加压素敏感。此外，加压素系统对乙醇和雌二醇都很敏感。目的3将测试V1a受体拮抗剂阻断乙醇诱导的条件性伴侣偏好的能力。总而言之，这些研究是了解小鼠滥用药物和社会纽带的重要第一步。 与公共健康相关：饮酒是一种社交消遣。尤其是在青少年中，有饮酒的朋友会增加饮酒行为。相反的情况也是如此。也就是说，饮酒促进了社会联系。社会诱导的饮酒和酒精诱导的社会纽带共同创造了一个潜在危险的正反馈循环，意味着在社会环境中过渡到不健康的饮酒模式。在年轻女性中，雌激素可能会加剧这种影响。这项拟议的研究将调查乙醇诱导的社会偏好以及卵巢类固醇激素对雌性小鼠的影响。

DESCRIPTION (provided by applicant): Drinking behavior and social context are intimately intertwined, particularly among young adults. Peer relations can promote drinking. At the same time, alcohol consumption promotes social bonding, as in the popular concept of a "drinking buddy". Ultimately, to combat unhealthy patterns of social drinking, it is important to understand how ethanol shapes the neurochemistry of affiliative behavior. We have developed a mouse model of conditioned partner preference, and we have obtained pilot data to demonstrate ethanol (EtOH)-induced social preference in female mice. Conditioned partner preference is similar to conditioned place preference, but it incorporates social aspects of approach, recognition, and affiliation. This has relevance to drinking behavior in humans. In our pilot studies thus far, female mice prefer conspecifics with whom they have previously been intoxicated. There is a further interaction of EtOH and estradiol to promote social preference, since EtOH-induced partner preference is enhanced in estrogen- treated ovariectomized females (OVX+E) vs ovariectomized females without estrogen (OVX). The proposed studies will use C57Bl/6 female mice to extend our initial observations. Aim 1a will determine the range of EtOH doses which facilitate conditioned partner preference in OVX, OVX+E, and OVX+E females with progesterone. Aim 1b will examine sex differences in EtOH- induced conditioned partner preference by testing orchidectomized males with and without testosterone. Aim 2 will expand the conditioned partner preference model to test the effects of other drugs of abuse (amphetamines, morphine) on social bonding. Finally, Aim 3 will begin to explore underlying mechanisms for EtOH-induced conditioned partner preference. In this regard, pair bonding and affiliative behavior are sensitive to vasopressin mediated through the vasopressin V1a receptor. Furthermore, the vasopressin system is sensitive to both EtOH and estradiol. Aim 3 will test the ability of a V1a receptor antagonist to block EtOH-induced conditioned partner preference. Together, these studies represent an essential first-step to understand substance abuse and social bonding in mice. PUBLIC HEALTH RELEVANCE: Drinking is a social pastime. Especially among teens, having friends who drink increases drinking behavior. The opposite is also true. That is, drinking promotes social connection. Together, socially-induced alcohol consumption and alcohol-induced social bonding create a potentially-dangerous positive feedback loop with implications for transitioning to unhealthy drinking patterns in social settings. In young women, estrogens may intensify this effect. The proposed studies will investigate ethanol-induced social preference and the effects of ovarian steroid hormones in female mice.