Adolescence, Puberty and Sex Differences: Ethanol Intake, Sensitivity and Stress

青春期、青春期和性别差异：乙醇摄入量、敏感性和压力

• 批准号: 7845599
• 负责人: LINDA PATIA SPEAR
• 金额: $ 33.21万
• 依托单位: STATE UNIVERSITY OF NY,BINGHAMTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7845599
• 关键词: Acute; Address; Adolescence; Adolescent; Adult; Age; Alcohol abuse; Alcohol consumption; Alcoholism; Alcohols; Animal Model; Animals; Attenuated; Behavior; Behavioral; Biological Factors; Brain; Characteristics; Cognitive; Consumption; Data; Dependence; Development; Ethanol; Female; Goals; Gonadal Hormones; Gonadal Steroid Hormones; Growth; Health; Hormonal; Hormones; Human; Impairment; Intake; Pattern; Perinatal; Physiological; Play; Prevention strategy; Puberty; Rattus; Relative (related person); Reporting; Research; Role; Sex Characteristics; Sexual Development; Stress; Testing; Time; Woman; Work; Youth; acute stress; alcohol effect; alcohol response; alcohol sensitivity; alcohol use disorder; attenuation; binge drinking; boys; developmental disease; drinking; drinking onset; early adolescence; experience; girls; implantation; indexing; male; men; neural patterning; neurobehavioral; relating to nervous system; sex; sobriety; social; stressor; young adult

DESCRIPTION (provided by applicant): Women have been excluded or underrepresented in much past research examining alcohol use and dependence. Yet, the research available has found women to differ from men in their alcohol drinking patterns and their sensitivity to various consequences of ethanol. These sex differences begin to emerge during adolescence and become more pronounced at maturity. While social, cultural and environmental influences undoubtedly contribute to the emergence of sex differences in alcohol intake and effects, biological factors also are likely to play an important role. Yet, despite the marked hormonal and neural changes associated with puberty and the other physiological transitions of adolescence, little is known of how these factors might contribute to the ontogeny of sex differences in ethanol intake and sensitivity. Determining the role of pubertal increases in gonadal hormones on the emergence of sex differences in alcohol consumption and consequences is ethically challenging in humans, but can be approached using animal models that share with human adolescents certain basic age-typical similarities in hormonal, neural, and behavioral characteristics. The proposed work will use a simple animal model of adolescence in the rat to examine the role of pubertal increases in gonadal hormones in both males and females on the emergence of sex differences in ethanol intake and consequences. Given mounting evidence that pubertal rises in gonadal steroids can exert organizational effects on the brain to support the differentiation of certain sex-typical behaviors at puberty, both organizational as well as activational (direct hormone-stimulated) effects of gonadal hormones will be explored. This will be accomplished via gonadectomizing animals either pre-pubertally or in adulthood, and hormone replacement beginning either at puberty or maturity. Focusing on alcohol-related sex differences that begin to emerge during the adolescent period and become marked in adulthood, the proposed studies will assess both organizational and activational effects of the rise in gonadal hormones at puberty on expression of sex differences in ethanol intake, ethanol sensitivity (indexed by ethanol-induced social suppression) and ethanol stress interactions. Despite the increasing emphasis on alcoholism as a developmental disorder, little is known of the potential role of the rise in pubertal hormones in promoting the emergence of sex-typical patterns of alcohol use, consequences and abuse. The proposed work will address this considerable gap in our understanding, data that should help inform the development of sex-relevant strategies for prevention, identification, and treatment of alcohol use disorders among youth and young adults.

描述（由申请人提供）：在过去的研究中，妇女被排除或不足，研究了酒精使用和依赖。然而，可用的研究发现，女性在饮酒方式上与男性有所不同，以及她们对乙醇各种后果的敏感性。这些性别差异在青春期开始出现，并且在成熟时变得更加明显。尽管社会，文化和环境影响无疑导致了酒精摄入和影响性别差异的出现，但生物学因素也可能起着重要作用。然而，尽管与青春期以及青春期的其他生理过渡相关的激素和神经变化显着，但对这些因素可能如何促成乙醇摄入和敏感性的性别差异的本体发育范围知之甚少。确定促性腺激素中青春期增长对饮酒和后果在人类中的性别差异出现的作用在人类中具有挑战性，但可以使用与人类青少年共享某些基本年龄典型的相似性在激素，神经和行为特征方面进行的动物模型。拟议的工作将使用大鼠中的青春期动物模型来检查男性和女性在性腺激素中青春期增加的作用，这些动物在乙醇摄入和后果中的性别差异出现。鉴于越来越多的证据表明，性腺类固醇中的青春期升高可以对大脑产生组织影响，以支持青春期某些性典型行为的分化，包括组织和激素（直接激素刺激）的性腺激素作用。这将通过前或成年后的雌性切除动物来实现，以及始于青春期或成熟的激素替代。拟议的研究专注于青春期开始出现并在成年期开始出现的性别差异，该研究将评估青春期在青春期激素升高对乙醇摄入乙醇摄入，乙醇敏感性表达性差异表达的组织和激活的效果（乙醇诱导的社交抑制作用）和乙醇诱导的乙醇互动。尽管越来越重视酒精中毒是一种发育障碍，但对青春期荷尔蒙在促进酒精使用，后果和滥用性的性典型模式中的出现中的潜在作用鲜为人知。拟议的工作将解决我们的理解中的这一巨大差距，这些数据应有助于告知与青年和年轻人对酒精使用障碍的预防，识别和治疗相关的性别策略的发展。