Ethanol-induced conditioned partner preference in mice

描述（由申请人提供）：饮酒行为与社会环境密切相关，尤其是在年轻人中。同伴关系可以促进饮酒。与此同时，饮酒促进了社会联系，比如流行的“酒友”概念。最后，为了对抗不健康的社交饮酒模式，重要的是要了解乙醇是如何塑造亲密行为的神经化学。我们已经建立了一个小鼠的条件伴侣偏好模型，我们已经获得了试点数据来证明乙醇（EtOH）诱导雌鼠的社会偏好。条件伴侣偏好类似于条件地点偏好，但它包含了方法、认可和隶属关系的社会方面。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，雌性老鼠更喜欢与它们以前陶醉过的同种老鼠。EtOH和雌二醇的进一步相互作用促进了社会偏好，因为EtOH诱导的伴侣偏好在雌激素治疗的卵巢切除雌性（OVX+E）中比在没有雌激素的卵巢切除雌性（OVX）中增强。本研究将使用C57Bl/6雌性小鼠来扩展我们的初步观察。目的1a将确定孕激素对OVX、OVX+E和OVX+E女性条件性伴侣偏好的EtOH剂量范围。Aim 1b将通过测试睾丸激素和非睾丸激素的睾丸切除雄性，研究EtOH诱导的条件伴侣偏好的性别差异。目标2将扩展条件伴侣偏好模型，以测试滥用其他药物（安非他明、吗啡）对社会联系的影响。最后，Aim 3将开始探索etoh诱导条件伴侣偏好的潜在机制。在这方面，通过抗利尿激素V1a受体介导的抗利尿激素对配对结合和亲和行为很敏感。此外，抗利尿激素系统对EtOH和雌二醇都很敏感。目的3将测试V1a受体拮抗剂阻断etoh诱导的条件伴侣偏好的能力。总之，这些研究代表了理解药物滥用和小鼠社会联系的重要的第一步。

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.