Adolescent Oxycodone Exposure on Oxycodone Reinforcement and Reward Neurocircuitry in Adulthood

青少年羟考酮暴露对成年期羟考酮强化和奖励神经回路的影响

• 批准号: 10447174
• 负责人: Sheketha Renay Hauser
• 金额: $ 7.93万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10447174
• 关键词: 17 year old; Acute; Adolescence; Adolescent; Adult; Affect; Age; Animal Model; Applications Grants; Behavior; Corpus striatum structure; Data; Development; Dopamine; Drug Addiction; Drug Exposure; Elderly; Exposure to; Future; Gender; Goals; Grant; Hormonal Change; Intervention; Intravenous; Knowledge; Long-Term Effects; Measures; Molecular; Neurobiology; Nucleus Accumbens; Oral; Oxycodone; Pathway interactions; Pharmaceutical Preparations; Preventive; Procedures; Property; Psychological reinforcement; Rewards; Self Administration; Testing; Time; United States Substance Abuse and Mental Health Services Administration; data modeling; drug of abuse; drug reinforcement; emerging adulthood; mesolimbic system; neural circuit; neuroadaptation; opioid use disorder; pre-clinical; prescription opioid; prescription opioid misuse; response; reward circuitry

ABSTRACT: Adolescence is one of the most vulnerable stages for the long-term effects of drugs of abuse and an estimated 3.4 million from adolescence have misused prescription opioids in the past year, with 3.5% of them being in early/mid stage of adolescents (12 -17 years old) and 7.1% of them being in the late adolescence to emerging adulthood stage (ages 18-25) (Substance Abuse and Mental Health Services Administration, 2017). Early adolescent initiation of prescriptions opioids is more likely to result in subsequent prescription opioid misuse in adulthood than late adolescent initiation (McCabe et al., 2007). Therefore, there is a need to better understand the long-term neurobiological consequences that misuse of prescription opioids in early/mid and late adolescence may have in adulthood in order to develop unique interventions. Oxycodone is one of the most commonly misused prescription opioids among adolescents. However, there is a substantial gap in knowledge about the long-term neurobiological consequences of adolescence exposure to oxycodone on reward-related behaviors in adulthood. The use of pre-clinical animal models can help to understand the effects of adolescent exposure to oxycodone on adult mesolimbic reward pathway. The major goal of this small grant project (R03) is to obtain proof of concept data to show that adolescent oxycodone exposure leads to a persistent increase in reinforcing properties/dopamine release in adulthood. Therefore, the overall objectives are to determine the effects of early and late adolescence exposure to oxycodone on drug reinforcement and dopamine release in nucleus accumbens in adulthood and assess if there are differential effects between early and late adolescence exposure. Since the early and late adolescence drug exposure will have differential effects on the neurobiology of reward circuits due to hormonal changes (Spears, 2000; 2015), we will utilize two time-points of adolescence exposure. This proposal will utilize state-of-the-art procedures to elucidate how adolescence exposure alters reinforcing properties of oxycodone within the mesolimbic dopamine system. This is a highly significant project that will provide first data on how adolescent exposure to oxycodone will have long-lasting effects on VTA rewarding properties in adulthood. Once we establish this phenomenon in this model, the data will be used to further understand the persistent changes in reward circuitry and molecular mechanisms in future R01 application.

抽象的： 青春期是最容易受到滥用药物长期影响的阶段之一，估计 去年，有 340 万名青少年滥用处方阿片类药物，其中 3.5% 青少年早中期（12岁-17岁），其中7.1%处于青春期后期至初露头期 成年阶段（18-25 岁）（药物滥用和心理健康服务管理局，2017 年）。早期的 青少年开始使用处方阿片类药物更有可能导致随后的处方阿片类药物滥用 成年期比青春期后期开始（McCabe 等，2007）。因此，有必要更好地了解 早期/中期和晚期滥用处方阿片类药物的长期神经生物学后果 青春期可能会在成年后制定独特的干预措施。羟考酮是最有效的药物之一 青少年中经常滥用处方阿片类药物。但知识上存在很大差距 关于青春期接触羟考酮对奖赏相关的长期神经生物学后果 成年后的行为。使用临床前动物模型可以帮助了解青少年的影响 成人中脑边缘奖赏途径中暴露于羟考酮。该小额赠款项目的主要目标（R03） 是为了获得概念验证数据以表明青少年羟考酮暴露会导致持续增加 增强成年后的特性/多巴胺释放。因此，总体目标是确定 青春期早期和晚期接触羟考酮对药物强化和多巴胺释放的影响 成年期的伏隔核并评估早期和晚期之间是否存在差异效应 青春期暴露。由于青春期早期和晚期的药物暴露会对身体产生不同的影响。 由于荷尔蒙变化引起的奖励回路的神经生物学（Spears，2000；2015），我们将利用两个时间点 青春期的暴露。该提案将利用最先进的程序来阐明青春期如何 暴露会改变中脑边缘多巴胺系统内羟考酮的增强特性。这是一个高度 这是一项重要的项目，将提供有关青少年接触羟考酮如何产生持久影响的第一批数据 对成年期 VTA 奖励特性的影响。一旦我们在这个模型中建立了这种现象，数据 将用于进一步了解奖励回路和分子机制的持续变化 未来的R01应用。