Impulsivity and reward in adult rats exposed to alcohol during adolescence

青春期暴露于酒精的成年大鼠的冲动和奖赏

• 批准号: 8318924
• 负责人: ATHINA MARKOU
• 金额: $ 34.82万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8318924
• 关键词: ARHGEF5 gene; Abstinence; Acute; Adolescence; Adolescent; Adult; Affect; Alcohol abuse; Alcohol consumption; Alcoholism; Amygdaloid structure; Anhedonia; Applications Grants; Area; Attention; Behavior; Behavioral; Brain; Brain Injuries; Chronic; Cognitive deficits; Corpus striatum structure; Decision Making; Development; Dopamine; Ethanol; Exhibits; Habenula; High Prevalence; Hippocampus (Brain); Human; Hypersensitivity; Immunohistochemistry; Impulsive Behavior; Impulsivity; Knowledge; Lead; Long-Term Effects; Measures; Mental Depression; Mental Health; Modeling; National Institute on Alcohol Abuse and Alcoholism; Neurobiology; Neurotransmitters; Nucleus Accumbens; Performance; Predisposition; Principal Investigator; Probability; Procedures; Rattus; Reaction Time; Research Personnel; Rewards; Self Stimulation; Serotonin; Stress; Structure; System; Testing; Ventral Tegmental Area; Withdrawal; adolescent alcohol exposure; alcohol effect; alcohol exposure; binge drinking; critical period; design; discounting; frontal lobe; maternal separation; neurochemistry; neuromechanism; neuropathology; neurotoxic; premature; problem drinker; public health relevance; resilience; response; reward circuitry; reward processing; social; stressor; transmission process; underage drinking

DESCRIPTION (provided by applicant): This grant application is in response to NIAAA announcement RFA-AA-10-006 entitled "Neurobiology of adolescent drinking in adulthood" (NADIA), and is a part of a Consortium of researchers investigating broad spectrum behavioral and neuropathological changes during adulthood after adolescent ethanol (EtOH) exposure. There is high prevalence of binge drinking among adolescents. Adolescence is a critical period for brain development that is particularly vulnerable to the neurotoxic effects of EtOH. Although some adolescent and adult alcoholics show deficits in attention and increased impulsivity, it is not known whether these behavioral alterations preceded or are the result of alcohol abuse. Increased impulsivity during adolescence in general may partially be attributed to hypersensitivity of the reward system in the adolescent brain, a system whose functioning may be altered by excessive alcohol drinking in adolescence. In addition, considering that the reward circuitry also regulates responses to stress, underage drinking may also alter responses to stressors. Finally, underage drinking is likely to alter dopaminergic (DA) and serotonergic (5- HT) transmitter systems involved in impulsivity, reward processes, and stress responsivity. Adolescent intermittent ethanol (AIE) exposure in rats models several aspects of underage binge drinking in humans. The long-term effects of adolescent EtOH exposure on attention, impulsivity, brain reward function and responses to stress, as well as the effects of alcohol challenges on these behaviors during adulthood remain largely unknown. The proposed studies will fill this gap in knowledge by investigating the long-term impact of AIE on attention and impulsivity (Aim 1), impulsive and risky decision-making (Aim 2), brain reward function and stress responsiveness (Aim 3), and the neurochemical changes in DA and 5-HT transmission likely to be involved in these behavioral alterations (Aim 4) in rats. It is hypothesized that AIE will result in a neuropathology of the DA and 5-HT corticolimbic and striatal brain areas that will manifest itself as impaired attention, increased impulsivity, poor decision-making, reward deficits, and altered responses to stressors during adulthood. These findings may lead to the discovery of behavioral and neurochemical targets for the discovery of treatments to assist people affected by underage drinking who exhibit poor decision-making, highly impulsive behaviors, mental health problems, such as depression/anhedonia, and/or excessive alcohol drinking in adulthood. PUBLIC HEALTH RELEVANCE: Adolescent exposure to alcohol may induce severe long-term brain damage that may result in profound behavioral and cognitive deficits that impair day-to-day function in adulthood. Further, such abnormalities may lead to alcoholism and exacerbate responses to stressors. This project will identify potential behavioral and neuropathological mechanisms in adulthood resulting from alcohol exposure in adolescence, and thus lead to the design.

描述（由申请人提供）：该赠款申请是对NIAAA公告RFA-AA-10-006的响应，标题为“成年后青春期饮酒的神经生物学”（Nadia），是研究源自源自乙醇乙醇元素的广泛行为和神经病理学变化的研究人员的一部分。青少年之间的暴饮暴食率很高。青春期是脑发育的关键时期，特别容易受到ETOH神经毒性作用的影响。尽管某些青少年和成人酗酒者的注意力和冲动性增加了，但尚不清楚这些行为改变是在之前的，还是由于酗酒而导致的。通常，在青春期的冲动性增加可能部分归因于青春期大脑中奖励系统的超敏反应，该系统的功能可能会因青春期过量饮酒而改变。此外，考虑到奖励电路还调节对压力的反应，未成年饮酒也可能会改变对压力源的反应。最后，未成年人饮酒可能会改变涉及冲动性，奖励过程和压力反应性的多巴胺能（DA）和血清素能（5-HT）发射器系统。大鼠的青少年间歇性乙醇（AIE）暴露于人类未成年人的饮酒的几个方面。青少年ETOH暴露对注意力，冲动性，大脑奖励功能和对压力的反应以及酒精挑战对这些成年行为的影响的长期影响仍然在很大程度上未知。拟议的研究将通过研究AIE对注意力和冲动性的长期影响（AIM 1），冲动和风险的决策（AIM 2），大脑奖励功能和压力反应性（AIM 3）以及DA和5-HT传播可能参与这些行为改变的DA和5-HT的神经化学变化（AIM 4），来填补这一差距。假设AIE将导致DA和5-HT皮质旁骨和纹状体大脑区域的神经病理学，这些神经病理学会表现为受损，冲动性增加，决策不良，奖励缺陷，奖励缺陷以及对压力因素的反应改变。这些发现可能会导致发现行为和神经化学靶标，以发现治疗方法，以帮助受未成年人饮酒影响的人们，这些人表现出不良的决策，高度冲动的行为，心理健康问题，例如抑郁症/Anhedonia和/或成年期间的饮酒过量。 公共卫生相关性：青少年暴露于酒精可能会引起严重的长期脑损伤，这可能导致行为和认知缺陷严重，从而损害了成年后日常功能。此外，这种异常可能导致酒精中毒并加剧对压力源的反应。该项目将在青春期饮​​酒导致的成年期间确定潜在的行为和神经病理学机制，从而导致设计。