Alcohol, Puberty, and Adolescent Brain Development

酒精、青春期和青少年大脑发育

• 批准号: 8493909
• 负责人: Cynthia M Kuhn
• 金额: $ 31.03万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-15 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8493909
• 关键词: Abnormal coordination; Adolescence; Adolescent; Adult; Age; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohols; Androgens; Animals; Behavioral; Biological; Biological Factors; Blood; Brain; Characteristics; Development; Endocrine; Estradiol; Estrogen Replacements; Estrogens; Estrous Cycle; Ethanol; Ethanol dependence; Female; Gender; Gonadal Steroid Hormones; Heavy Drinking; Hormonal; Hormones; Individual; Individual Differences; Male Adolescents; Measures; Mediator of activation protein; Modeling; Motor; Pattern; Phase; Phenotype; Plasma; Prevention; Prevention program; Prevention strategy; Progesterone; Protocols documentation; Puberty; Rattus; Relative (related person); Risk Factors; Rodent Model; Role; Sedation procedure; Sex Characteristics; Statistical Models; Taste Perception; Testing; Testosterone; Woman; alcohol effect; alcohol preferring rats; alcohol sensitivity; behavior measurement; binge drinking; boys; design; drinking; early adolescence; effective therapy; girls; insight; male; men; postnatal; prepuberty; problem drinker; sedative; sex; social; statistics; treatment program; treatment strategy; young adult; young man; young woman

DESCRIPTION (provided by applicant): Adolescents are vulnerable to the development of alcohol abuse. Insensitivity to the sedative effects of ethanol may contribute to this vulnerability. Insensitivity to the use-limiting effects of ethanol like sedation is a common risk factor for the development of alcohol abuse. However, the way that developmental state, individual differences and hormonal state contribute to ethanol insensitivity and the trajectory into alcohol abuse is unknown. The purpose of the present proposal is to test three interrelated hypothesis: (1) that insensitivity to use-limiting effects of ethanol are characteristic of adolescents of both sexes (2) that individual differences in ethanol sensitivity predict ethanol consumption in both adolescents and adults independently of developmental status, (3) that pubertal changes in hormone levels will influence both ethanol sensitivity and ethanol consumption: specifically the emergence of estrous cycles will introduce stimulatory (estradiol) and inhibitory (progesterone) influences on ethanol use-limiting effects and ethanol consumption in females while organizational effects of androgen may cause irreversible changes in male drinking patterns. We plan to: (1) evaluate the contribution of gonadal steroids to the use-limiting effects of ethanol sensitivity and ethanol intake during adolescence and (3) assess the contribution of individual differences in ethanol sensitivity and gonadal steroids to ethanol intake during adolescence in male and female rats. We will measure ethanol-induced sedation, motor incoordination and conditioned taste aversion (CTA) on postnatal (PN) day 30, 45 and 60 and 90 after sham and active gonadectomy prepubertally (PN 25) or post-pubertally (PN 55), and after estrogen, progesterone and testosterone replacement. For Specific Aim 2, rats will be characterized for ethanol-induced CTA, and then entered into an ethanol drinking protocol through puberty (start days 30, 45, 60). We will compare ethanol intake in gonadally intact animals and in animals after pre- or postpubertal gonadectomy and hormone replacement. The contribution of ethanol sensitivity, sex, age and hormone levels to three phases of ethanol drinking (forced, voluntary and rebound) will be modeled using multivariate statistics. Identifying behavioral characteristics that predispose individuals to alcohol abuse can facilitate the development of effective treatment and prevention programs. These findings will provide insight into influence of puberty on the development of alcohol consumption. This information will help us develop more targeted prevention and treatment strategies for young men and women alcoholics.

描述（由申请人提供）：青少年容易酗酒。对乙醇的镇静作用不敏感可能会导致这种脆弱性。对乙醇（如镇静）的使用限制作用不敏感是形成酒精滥用的常见危险因素。然而，发育状态、个体差异和激素状态如何导致乙醇不敏感以及酒精滥用的轨迹尚不清楚。本提案的目的是检验三个相互关联的假设：（1）对乙醇使用限制效应不敏感是男女青少年的特征（2）乙醇敏感性的个体差异独立预测青少年和成人的乙醇消耗量(3) 青春期激素水平的变化将影响乙醇敏感性和乙醇消耗：特别是发情周期的出现将对乙醇产生刺激性（雌二醇）和抑制性（黄体酮）影响女性的使用限制效应和乙醇消耗，而雄激素的组织效应可能会导致男性饮酒模式发生不可逆转的变化。我们计划：（1）评估性腺类固醇对青春期乙醇敏感性和乙醇摄入量的使用限制影响的贡献；（3）评估男性青春期乙醇敏感性和性腺类固醇的个体差异对乙醇摄入量的贡献和雌性老鼠。我们将在假手术和青春期前 (PN 25) 或青春期后 (PN 55) 主动性腺切除术后的产后 (PN) 第 30、45、60 和 90 天测量乙醇诱导的镇静、运动不协调和条件性味觉厌恶 (CTA)，以及补充雌激素、孕激素和睾酮后。对于具体目标 2，将对大鼠进行乙醇诱导的 CTA 表征，然后在整个青春期（第 30、45、60 天开始）进入乙醇饮用方案。我们将比较性腺完整的动物和青春期前或后性腺切除和激素替代后的动物的乙醇摄入量。乙醇敏感性、性别、年龄和激素水平对乙醇饮用三个阶段（强迫、自愿和反弹）的影响将使用多元统计数据进行建模。识别导致个人酗酒的行为特征可以促进有效治疗和预防计划的制定。这些发现将有助于深入了解青春期对饮酒发展的影响。这些信息将帮助我们为年轻男女酗酒者制定更有针对性的预防和治疗策略。