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: 8032643
• 负责人: ATHINA MARKOU
• 金额: $ 36.37万
• 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/8032643
• 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; 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）：该资助申请是为了响应NIAAA公告RFA-AA-10-006，标题为“成年期青少年饮酒的神经生物学”（NADIA），是研究人员联盟的一部分，研究青少年酒精（EtOH）暴露后成年期的广谱行为和神经病理变化。青少年中酗酒的发生率很高。青春期是大脑发育的关键时期，特别容易受到EtOH的神经毒性影响。虽然一些青少年和成人酗酒者表现出注意力缺陷和冲动增加，但尚不清楚这些行为改变是酗酒之前还是酗酒的结果。一般来说，青春期冲动的增加可能部分归因于青春期大脑中奖励系统的过度敏感，该系统的功能可能因青春期过量饮酒而改变。此外，考虑到奖赏回路也调节对压力的反应，未成年人饮酒也可能改变对压力源的反应。最后，未成年人饮酒可能会改变多巴胺能（DA）和5-羟色胺能（5- HT）递质系统，这些递质系统涉及冲动、奖励过程和应激反应。大鼠的青春期间歇乙醇暴露模拟了人类未成年人酗酒的几个方面。青少年接触EtOH对注意力、冲动、大脑奖励功能和压力反应的长期影响，以及酒精挑战对成年期这些行为的影响，在很大程度上仍然未知。拟开展的研究将通过调查AIE对大鼠注意力和冲动性（Aim 1）、冲动和冒险决策（Aim 2）、脑奖励功能和应激反应（Aim 3）的长期影响，以及可能参与这些行为改变（Aim 4）的DA和5-HT传递的神经化学变化，填补这一知识空白。假设AIE会导致DA和5-羟色胺皮质边缘和纹状体脑区域的神经病理学，表现为成年期注意力受损、冲动增加、决策不良、奖励缺陷和对压力源的反应改变。这些发现可能会导致行为和神经化学靶点的发现，从而发现治疗方法，以帮助那些表现出决策不良、高度冲动行为、精神健康问题（如抑郁/快感缺乏和/或成年后过度饮酒）的未成年人。