THC Affects the Development of Executive Function

THC 影响执行功能的发展

• 批准号: 6887928
• 负责人: DIANA L DOW-EDWARDS
• 金额: $ 29.51万
• 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/6887928
• 关键词: adolescence (12-20); age difference; autoradiography; cannabinoids; child (0-11); cognition; deoxyglucose; developmental neurobiology; embryo /fetus toxicology; 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）： 在最近的综述中，弗里德（Fried）和史密斯（Smith）总结了产前大麻对儿童认知功能的影响，这是对执行功能（EF）的负面影响。除了基本的视觉观察能力外，还需要计划，集成，分析和综合的任务受到大麻烟妇女的损害。由于这些能力在个人的早期生活中发展，因此该提案将解决大麻主要的精神活性成分，Delta9四氢大麻酚或Delta9THC的影响，对老鼠执行功能的这些方面的发展。将研究四个曝光周期，并使用1）避免主动位置确定EF，2）空间导航（延迟的径向臂迷宫），3）被动回避和4）一种新的注意力测试。总体假设是，在开发这些认知任务中涉及的电路（MPFCX，Hippocampus，MD Thalamus，VTA等）中，Delta9THC暴露会损害执行功能的特定方面。 AIM I.确定产前delta9THC对成年后评估的EF任务中的性能的影响，并与成人的慢性Delta9THC暴露相比。 目标II。确定早期产后（与人类妊娠后半段有关）的影响，DELTA9THC暴露对成年期EF任务的执行。 目标三。确定童年/青春期早期delta9THC暴露对成年期EF任务中表现的影响。 目标IV。确定青少年晚期/年轻成人Delta9THC暴露对成年期EF任务中的性能的影响。 AIM V.确定使用脱氧葡萄糖从事EF任务的正常大鼠中发生的功能耦合模式，以及在关键开发期间的delta9THC暴露是否会改变功能耦合模式。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。 总之，这些研究将确定早期生命期间的Delta9THC暴露对执行功能的影响，以及当受试者从事认知任务时，这些暴露是否会改变大脑中功能耦合的模式。