Ethanol-induced conditioned partner preference in mice

乙醇诱导小鼠条件性伴侣偏好

• 批准号: 8383404
• 负责人: RUTH I. WOOD
• 金额: $ 20.5万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8383404
• 关键词: Adolescence; Affect; Alcohol abuse; Alcohol consumption; Alcohols; Amphetamines; Area; Characteristics; Clinical; Consumption; Data; Dose; Drug usage; Estradiol; Estrogen Replacements; Estrogens; Ethanol; Feedback; Female; Friends; Future; Goals; Gonadal Steroid Hormones; Hormones; Human; Mediating; Microtus; Modeling; Morphine; Mus; Opiates; Orchiectomy; Ovarian Steroid Hormone; Pair Bond; Pattern; Pharmaceutical Preparations; Pilot Projects; Population; Progesterone; Puberty; Research; Rewards; Role; Sex Behavior; Sex Characteristics; Shapes; Social Behavior; Social Conditions; Social Environment; Substance Abuse Detection; Substance abuse problem; System; Teenagers; Testing; Testosterone; Time; V1a vasopressin receptor; Vasopressins; affiliative behavior; binge drinking; combat; d(CH2)5(Tyr(Me)(2))AVP; drinking; drinking behavior; drug of abuse; drug reward; male; mouse model; neurochemistry; neuromechanism; novel; novel strategies; peer; preference; receptor; reinforcer; relating to nervous system; response; social; social attachment; steroid hormone; young adult; young woman

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.

描述（由申请人提供）：饮酒行为和社会环境密切相关，特别是在年轻人中。同伴关系可以促进饮酒。与此同时，酒精消费促进了社会联系，如流行的"酒友"概念。最终，为了对抗不健康的社交饮酒模式，重要的是要了解乙醇如何塑造亲和行为的神经化学。我们已经开发了一个小鼠模型的条件伴侣偏好，我们已经获得了试点数据，以证明乙醇（EtOH）诱导的社会偏好的雌性小鼠。条件性伴侣偏好类似于条件性位置偏好，但它包含了接近、认可和归属等社会方面。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，雌性小鼠更喜欢与它们先前被麻醉的同类。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女性（OVX + E）中比在没有雌激素的卵巢切除女性（OVX）中增强。拟议的研究将使用C57B1/6雌性小鼠来扩展我们的初步观察。目的1a将确定促进OVX、OVX + E和OVX + E雌性孕激素条件性伴侣偏好的EtOH剂量范围。目的1b将通过测试切除睾丸的男性在有和没有睾酮的情况下，来检验乙醇诱导的条件性伴侣偏好的性别差异。目标2将扩展条件性伴侣偏好模型，以测试其他滥用药物（安非他明，吗啡）对社会联系的影响。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。在这方面，配对和亲和行为是敏感的加压素介导的加压素V1a受体。此外，加压素系统对EtOH和雌二醇都敏感。目的3将测试V1a受体拮抗剂阻断EtOH诱导的条件性伴侣偏好的能力。总之，这些研究代表了理解小鼠药物滥用和社会联系的重要第一步。 公共卫生相关性：饮酒是一种社交消遣。尤其是在青少年中，有喝酒的朋友会增加饮酒行为。反之亦然。饮酒促进社会联系。总之，社会诱导的酒精消费和酒精诱导的社会联系创造了一个潜在的危险的积极反馈循环，影响了社会环境中向不健康饮酒模式的转变。在年轻女性中，雌激素可能会加剧这种影响。这项研究将探讨乙醇诱导的社会偏好和卵巢类固醇激素对雌性小鼠的影响。