8/8 NADIA UO1 Adolescent Alcohol and Decision Making

8/8 NADIA UO1 青少年酒精与决策

• 批准号: 9762555
• 负责人: Paul E. M. Phillips
• 金额: $ 17.38万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9762555
• 关键词: Adolescence; Adolescent; Adult; Age; Agonist; Alcohol abuse; Alcohol consumption; Alcohols; Animals; Attitude; Behavior; Behavioral; Brain; Characteristics; Chemosensitization; Choice Behavior; Corpus striatum structure; Coupled; Data; Decision Making; Development; Disinhibition; Dopamine; Dose; Drug abuse; Drug usage; Ethanol; Exposure to; Future; Glutamates; Goals; Human; Impairment; Incidence; Individual; Life; Link; Longevity; Measures; Mediating; Midbrain structure; Modeling; Monitor; Neurobiology; Neurons; Pathway interactions; Periodicity; Pharmacology; Phase; Preparation; Process; Protocols documentation; Public Health; Rattus; Reporting; Risk; Risk-Taking; Scanning; Signal Transduction; Societies; Therapeutic; Time; Ventral Striatum; Ventral Tegmental Area; Wit; Work; addiction; adolescent alcohol exposure; alcohol exposure; alcohol use disorder; base; binge drinking; cholinergic; clinically relevant; critical period; dopamine system; dopaminergic neuron; experience; experimental study; in vivo; mature animal; mesolimbic system; neurochemistry; neurotransmission; pedunculopontine tegmentum; preference; public health relevance; receptor; response; reward processing; risk mitigation; transmission process; underage drinking

 DESCRIPTION (provided by applicant): Adolescent alcohol use remains a major public health concern due in part to evidence implicating the age of initial alcohol use as a strong predictor fo the development of alcohol use disorders in adulthood. Recent reports evaluating the impact of drug abuse on society conclude that alcohol ranks as the most harmful of all abused substances. In addition, despite continuing efforts to curb its use, alcohol remains the most commonly used and abused substance among adolescents. That such experience can be antecedent to problem drinking has been recognized for some time; that such experience may also have long-lasting effects on decision- making processes is a relatively recent consideration. Moreover, it has been suggested that such deficits in decision making may represent a vulnerability to addiction. Indeed, people who engage in binge drinking at an early age show later deficits in decision making and increased likelihood of developing alcohol abuse problems. However, interpretation of these reports in humans has remained challenging due to the difficulty in separating the specific consequences of early drug use on future behavior from pre-existing factors that may contribute throughout the lifespan. We have demonstrated that rats exposed to alcohol during adolescence make maladaptive, risky choices as adults. This impairment represents a unique vulnerability of the developing brain as we have also shown that adult rats given identical exposure do not show this deficit. Adolescence has been characterized as a time of heightened risk-taking behavior in humans. Moreover, adolescence is a critical period of maturation when brain development, including that of the mesolimbic dopamine (DA) system, may be disrupted by alcohol. Mesolimbic DA is implicated in multiple aspects of reward processing and risk preference is sensitive to manipulations of striatal phasic DA signaling. Indeed, we have shown that striatal phasic DA release in response to risky options relative to safe options is significantly increased in alcohol-exposed rats. Further, there is a relative disinhibition in DA signaling during adolescence itself. Therefore, an appealing theoretical approach has been to link maturational changes in DA systems with behavioral changes in decision making and to posit that early life alcohol use confers a neurobiological profile that promotes persistent maladaptive decision making into adulthood. However, our findings to date are based on low levels of exposure that model recreational alcohol use while one of the defining features of use in human adolescents is a high incidence of binge drinking. Thus, in this proposal we aim to expand the scope and clinical relevance of our work by examining the consequences of binge alcohol use, which predominates in adolescence and is achieved by the NADIA AIE protocol. We hypothesize that increased risk bias, characteristic of the adolescent period, is attributable to mesolimbic DA systems and that exposure to AIE alters these circuits, resulting in a circuit-specific potentiation of midbrain DA neuron activity and persistent maladaptive decision making in adulthood.

 描述（由适用提供）：青少年饮酒仍然是一个主要的公共卫生问题，部分原因是证据隐含了初始饮酒的年龄，这是在成年期的饮酒障碍发展的强大预测因素。评估药物滥用对社会的影响的最新报告中，酒精是所有滥用物质中最有害的。此外，继续努力遏制其使用，酒精仍然是青少年中最常用和滥用的物质。这种经验可能是饮酒的前提，已经认可了一段时间。这种经验也可能对决策过程产生长期影响，这是一个相对的考虑因素。此外，有人建议决策中的这种定义可能代表着成瘾的脆弱性。确实，在早期进行暴饮暴食的人后来定义了决策和增加酗酒问题的可能性。但是，由于难以将早期使用对未来行为的特定后果与可能在整个生命周期促成的预先存在的因素分离出来的具体后果，因此对人类中这些报告的解释仍然存在挑战。我们已经证明，在青少年期间暴露于酒精的大鼠是成年人的适应不良，冒险的选择。这种障碍代表了发展中大脑的独特脆弱性，因为我们还表明，给予相同暴露的成年大鼠没有显示这种防御。青少年被认为是人类冒险行为增加的时期。此外，青少年是一个至关重要的成熟时期，当脑发育（包括中唇多巴胺（DA）系统的脑发育）可能受到酒精的破坏。中唇DA在奖励处理的多个方面实施，风险偏好对纹状体阶段性DA信号的操纵敏感。实际上，我们已经表明，相对于安全选择的风险选择，纹状体阶段DA释放在酒精暴露的大鼠中显着增加。此外，那里 是青少年本身期间DA信号传导的相对抑制作用。因此，一种外观理论方法是将DA系统中的成熟变化与决策的行为变化联系起来，并分配早期寿命的饮酒赋予了神经生物学特征，该神经生物学特征促进了成年期持续的不良适应性决策。但是，迄今为止，我们的发现是基于对休闲饮酒建模的暴露水平低，而人类青少年使用的定义特征之一是暴饮暴食的高发生率。在这项建议中，我们旨在通过检查暴饮暴食的后果来扩大我们工作的范围和临床相关性，该饮酒的后果占青少年，并由Nadia aie方案实现。我们假设增加的风险偏见（青少年时期的特征）归因于中脑脱脂系统，并且暴露于AIE会改变这些电路，从而导致了中脑DA神经活动的特定电路潜力，并且在富裕中持续不良的不良疾病决策。