Effects of Adolescent Alcohol Exposure on Decision Making in Adult Rats

青少年酒精暴露对成年大鼠决策的影响

• 批准号: 8889174
• 负责人: HEATHER L TRANTHAM-DAVIDSON
• 金额: $ 17.02万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-10 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8889174
• 关键词: Acute; Address; Adolescence; Adolescent; Adolescent Development; Adult; Age-Months; Alcohol abuse; Alcohol consumption; Alcohols; Animal Model; Area; Behavior; Behavior Control; Behavioral; Brain; Brain region; Catechols; Cell Nucleus; Cognition; Cognitive; Complex; Consumption; Data; Decision Making; Development; Dopamine; Dopamine Receptor; Electrophysiology (science); Environment; Enzymes; Epidemiology; Ethanol; Exhibits; Foundations; Goals; Health; High Prevalence; Human; Impaired cognition; Impairment; Impulsivity; Individual; Knowledge; Label; Laboratories; Lead; Life; Long-Term Effects; Medial; Mediating; Mentored Research Scientist Development Award; Mentors; Modeling; Neurobiology; Neurons; Outcome; Pattern; Phenotype; Play; Population; Prefrontal Cortex; Process; Public Health; Punishment; Rattus; Recording of previous events; Research; Research Personnel; Research Training; Rewards; Risk; Risk Behaviors; Risk-Taking; Role; Slice; Solid; Staging; Structure; Synapses; Testing; Tracer; Training; Transferase; adolescent alcohol; adolescent alcohol abuse; adolescent alcohol exposure; alcohol exposure; alcohol research; behavioral study; brain behavior; career; career development; cellular targeting; cognitive control; cognitive function; critical period; discounting; dopamine transporter; early adolescence; executive function; experience; extracellular; flexibility; hippocampal pyramidal neuron; improved; indexing; interdisciplinary approach; nerve supply; neuropathology; neurotransmission; novel; patch clamp; programs; receptor function; research study; response; stem; trait; underage drinking

DESCRIPTION (provided by applicant): This is an application for a Mentored Research Scientist Development Award (K01) to support the career development of Dr. Heather Trantham-Davidson as an independent academic investigator in alcohol research. The candidate is an early-stage investigator with previous training in the area of prefrontal cortical function and is relatively new to the alcohol field. A comprehensive mentoring and research plan is presented that will provide training in the neurobiology of adolescent alcohol abuse and its long-term effects on brain and behavior. The career and research training the applicant will receive will be overseen by a strong mentoring team and supported by strong institutional commitment to the candidate's career development. The research proposed is an extension of the applicant's recent studies in the mentor's laboratory examining the effects of adolescent alcohol exposure on the prefrontal cortex (PFC) of adult rats. The proposed research plan will take full advantage of the mentoring team and environment to allow the candidate to develop a research program that is at the forefront of the adolescent alcohol field. The PFC is a brain region that is critically involved in cognitive function and inhibitory control, and adolescence represents a critical period of continued PFC development that parallels the maturation of these functions. Alcohol drinking typically begins during adolescence when consumption of large quantities, in binge-like episodic patterns, is common. Alterations in PFC function are associated with increased likelihood to engage in risky behaviors and poor decision-making. Epidemiological evidence suggests that adolescent alcohol exposure may result in life-long deficits in cognitive control of behavior that may stem from disruption of the normal developmental trajectory of the PFC. However, the specific cellular targets in the adult PFC that are disrupted by adolescent alcohol abuse remain unclear and will be elucidated by the experiments outlined in this proposal. The overarching hypothesis is that adolescent alcohol exposure produces a neuropathology of the PFC that manifests in the adult as deficits in dopamine modulation of deep-layer pyramidal neurons of the prelimbic subregion and its projections to subcortical nuclei. This hypothesis will be tested using a multidisciplinary approach that includes patch-clamp slice electrophysiology and behavioral studies involving operant tasks to assess risky decision-making. These studies will determine the cellular mechanisms of persistent cognitive dysfunction following adolescent alcohol exposure, yield novel and exciting new findings, and significantly advance our understanding of the cellular mechanisms mediating the effect of adolescent alcohol exposure on cognitive function in the adult. Together, this training and research plan will provide a solid foundation upon which the applicant can build an independent research program.

描述（由申请人提供）：这是一份指导研究科学家发展奖（K01）的申请，以支持Heather Trantham-Davidson博士作为酒精研究的独立学术研究者的职业发展。候选人是一名早期的研究者，之前在前额皮质功能领域受过训练，对酒精领域相对较新。提出了一项全面的指导和研究计划，将提供青少年酒精滥用及其对大脑和行为的长期影响的神经生物学方面的培训。申请人将接受的职业和研究培训将由一个强大的指导团队监督，并由强有力的机构承诺支持候选人的职业发展。该研究是申请人最近在导师的实验室研究青少年酒精暴露对成年大鼠前额叶皮质（PFC）的影响的延伸。建议的研究计划将充分利用师徒团队和环境，使候选人能够制定一个处于青少年酒精领域前沿的研究计划。PFC是一个与认知功能和抑制控制密切相关的大脑区域，青春期是PFC持续发展的关键时期，与这些功能的成熟平行。饮酒通常开始于青春期，在这个时期，大量饮酒，以类似狂欢的形式出现，是很常见的。PFC功能的改变与从事危险行为和不良决策的可能性增加有关。流行病学证据表明，青少年酒精暴露可能导致终身行为认知控制缺陷，这可能源于PFC正常发育轨迹的破坏。然而，成人PFC中被青少年酒精滥用破坏的特定细胞靶点仍不清楚，将通过本提案中概述的实验来阐明。最重要的假设是，青少年酒精暴露会导致PFC神经病变，在成人中表现为边缘亚区深层锥体神经元的多巴胺调节缺陷及其向皮层下核的投射。这一假设将采用多学科方法进行验证，包括膜片钳切片电生理学和涉及操作性任务的行为研究，以评估风险决策。这些研究将确定青少年酒精暴露后持续认知功能障碍的细胞机制，产生新的和令人兴奋的新发现，并显著推进我们对介导青少年酒精暴露对成人认知功能影响的细胞机制的理解。总之，这个培训和研究计划将为申请人建立一个独立的研究计划提供坚实的基础。