THC Affects the Development of Executive Function

THC 影响执行功能的发展

• 批准号: 7169728
• 负责人: DIANA L DOW-EDWARDS
• 金额: $ 2.96万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7169728
• 关键词: adolescence (12-20); age difference; autoradiography; cannabinoids; child (0-11); cognition; deoxyglucose; developmental neurobiology; embryo /fetus toxicology; executive function; functional ability; in situ hybridization; laboratory rat; marijuana abuse; neuroanatomy; neuropsychological tests; young adult human (21-34)

DESCRIPTION (provided by applicant): In a recent review, Fried and Smith summarized the effects of prenatal marijuana exposure on cognitive function in children as negatively impacting aspects of executive function (EF). Tasks that required planning, integration, analysis and synthesis in addition to basic visuoperceptual abilities were impaired in children of marijuana-smoking women. Since these abilities develop over the early life of an individual, this proposal will address the effects of marijuana's major psychoactive constituent, delta9 tetrahydrocannabinol or delta9THC, on the development of these aspects of executive function in the rat. Four exposure periods will be studied and EF will be determined using 1) Active Place Avoidance, 2) Spatial navigation (radial arm maze with delay), 3) passive avoidance and 4) a novel attentional test. The overall hypothesis is that delta9THC exposure during the development of the circuits involved in each of these cognitive tasks (the mPFCx, hippocampus, MD thalamus, VTA etc) will impair specific aspects of executive function. AIM I. Determine the effects of prenatal delta9THC on performance in EF tasks assessed in adulthood and compared to chronic delta9THC exposure in adults. AIM II. Determine the effects of early postnatal (relevant to the latter half of human pregnancy) delta9THC exposure on performance of EF tasks in adulthood. AIM III. Determine the effects of childhood/early adolescence delta9THC exposure on performance in EF tasks in adulthood. AIM IV. Determine the effects of late adolescent/young adult delta9THC exposure on performance in EF tasks in adulthood. AIM V. Determine the pattern of functional coupling that occurs in a normal rat engaged in an EF task using deoxyglucose and whether delta9THC exposure during critical periods of development will alter that pattern of functional coupling. In addition, the molecular underpinnings for these functional changes will be assessed using in situ hybridization histochemistry. Together, these studies will determine the effects of delta9THC exposure during early life on executive function and whether these exposures alter the pattern of functional coupling in brain when a subject is engaged in a cognitive task.

描述（由申请人提供）： 在最近的一篇评论中，弗里德和史密斯将产前大麻暴露对儿童认知功能的影响总结为对执行功能（EF）的负面影响。吸食大麻的妇女的孩子除了基本的视觉感知能力外，还需要计划、整合、分析和综合的任务受到损害。由于这些能力是在个体的早期发育过程中形成的，因此该提案将解决大麻的主要精神活性成分 delta9 四氢大麻酚或 delta9THC 对大鼠执行功能这些方面的发展的影响。将研究四个暴露周期，并使用 1) 主动场所回避、2) 空间导航（带延迟的径向臂迷宫）、3) 被动回避和 4) 新颖的注意力测试来确定 EF。总体假设是，在参与这些认知任务的回路（mPFCx、海马体、MD 丘脑、VTA 等）发育过程中接触 delta9THC 会损害执行功能的特定方面。 目的 I. 确定产前 delta9THC 对成年期评估的 EF 任务表现的影响，并与成人长期接触 delta9THC 进行比较。 目标二。确定产后早期（与人类妊娠后半期相关）delta9THC 暴露对成年期 EF 任务表现的影响。 目标三。确定童年/青春期早期 delta9THC 暴露对成年期 EF 任务表现的影响。 目标四。确定青少年晚期/年轻人 delta9THC 暴露对成年期 EF 任务表现的影响。 目的 V. 确定使用脱氧葡萄糖参与 EF 任务的正常大鼠中发生的功能耦合模式，以及在发育关键时期暴露 delta9THC 是否会改变该功能耦合模式。此外，将使用原位杂交组织化学评估这些功能变化的分子基础。 这些研究将共同​​确定生命早期接触 delta9THC 对执行功能的影响，以及当受试者从事认知任务时这些接触是否会改变大脑中的功能耦合模式。