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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

基本信息

批准号：
8718941
负责人：
ATHINA MARKOU
金额：
$ 33.46万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
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/8718941
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

项目摘要

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.

描述（由申请人提供）：本拨款申请是为了响应 NIAAA 公告 RFA-AA-10-006，标题为“青少年饮酒的神经生物学”(NADIA)，并且是调查青少年酒精 (EtOH) 暴露后成年期间广泛行为和神经病理学变化的研究人员联盟的一部分。青少年中酗酒的现象非常普遍。青春期是大脑发育的关键时期，特别容易受到乙醇的神经毒性作用。尽管一些青少年和成年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发生的还是酗酒的结果。一般来说，青春期冲动的增加可能部分归因于青少年大脑中奖赏系统的过敏，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涉及冲动、奖励过程和压力反应的多巴胺能 (DA) 和血清素能 (5-HT) 递质系统。大鼠青少年间歇性乙醇（AIE）暴露模拟了人类未成年人酗酒的几个方面。青少年接触乙醇对注意力、冲动、大脑奖赏功能和压力反应的长期影响，以及成年期间酒精挑战对这些行为的影响在很大程度上仍然未知。拟议的研究将通过调查 AIE 对注意力和冲动性（目标 1）、冲动和风险决策（目标 2）、大脑奖赏功能和压力反应性（目标 3）的长期影响，以及可能与这些行为改变有关的 DA 和 5-HT 传递的神经化学变化（目标 4）来填补这一知识空白。据推测，AIE 将导致 DA 和 5-HT 皮质边缘和纹状体大脑区域的神经病理学，表现为注意力受损、冲动增加、决策不佳、奖励缺陷以及成年期间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目标的发现，从而找到治疗方法，以帮助受未成年饮酒影响的人，这些人表现出决策不佳、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。