Lasting behavioral and neuroimaging consequences of adolescent exposure to cannabis smoke.

青少年接触大麻烟雾的持久行为和神经影像学后果。

• 批准号: 9091521
• 负责人: Adriaan Willem Bruijnzeel
• 金额: $ 22.28万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9091521
• 关键词: Abstinence; Address; Adolescence; Adolescent; Adult; Affect; Affective; Age; Agonist; Animal Model; Anxiety; Anxiety Disorders; Behavioral; Blood; Brain; Cannabinoids; Cannabis; Cerebrum; Chronic; Cognition; Cognitive; Cognitive deficits; Data; Decision Making; Development; Emotional; Employee Strikes; Exposure to; Female; Goals; Health; Hippocampus (Brain); Human; Incidence; Knowledge; Literature; Magnetic Resonance Imaging; Marijuana Dependence; Marijuana Smoking; Measures; Medical; Memory; Mental Depression; Methods; Modeling; Outcome; Play; Prefrontal Cortex; Prevalence; Public Policy; Publishing; Rattus; Reporting; Research; Rodent Model; Role; Route; Short-Term Memory; Smoking; Structural defect; System; Techniques; Testing; Tetrahydrocannabinol; Work; anxiety-like behavior; brain behavior; brain circuitry; brain volume; cannabinoid receptor; cognitive process; depressive symptoms; early onset; executive function; exposed human population; flexibility; male; marijuana use; marijuana user; negative affect; neurobehavioral; neuroimaging; programs; relating to nervous system; research study; spatial memory; white matter

DESCRIPTION (provided by applicant): Chronic cannabis use in humans is associated with a range of affective, cognitive, and neural alterations, including a higher incidence of depression and anxiety, deficits in memory and executive functions, and regional reductions in brain volume and white matter integrity. Emerging evidence indicates that these alterations are greater when cannabis use begins at an early age and can persist well into abstinence, indicating that adolescent cannabis exposure may have particularly deleterious effects on the developing brain. These findings are consistent with research in rodent models showing that administration of ¿9THC or other cannabinoid agonists during adolescence causes cognitive deficits and increased negative affect in adulthood. Notably, however, there is almost no research on the effects of adolescent exposure to cannabis smoke on neurobehavioral outcomes. The lack of such research is striking, not only because smoking is the preferred route of human cannabis use, but because cannabis smoke contains numerous cannabinoid and other compounds aside from ¿9THC, some of which are known to be psychoactive and may have lasting effects on the brain and behavior. Hence, in order to assess the causal impact of cannabis use, it is critical to employ a model that mimics the conditions of actual human exposure. The long-term goal of this research program is to determine how adolescent exposure to cannabis smoke affects adult emotional, cognitive, and brain structural/functional measures shown to be altered in human cannabis users. Important to this long-term goal, we have established a cannabis smoke exposure model in rats, which produces blood THC levels comparable to those found in humans and in which we have demonstrated cannabis dependence following chronic exposure. Building on these preliminary data, as well as published literature on cannabis users, our central hypothesis is that adolescent cannabis smoke exposure will cause deleterious effects on emotional and cognitive processing in adulthood that are accompanied by structural abnormalities in relevant brain circuitry. We will test this central hypothesis in a rat model by: 1) determining whether adolescent cannabis smoke exposure influences negative affect (measures of depression- and anxiety-like behavior) during adulthood; 2) determining whether adolescent cannabis smoke exposure influences multiple measures of memory and executive function in adulthood; 3) determining whether adolescent cannabis smoke exposure affects brain volume and white matter integrity during adulthood, using neuroimaging techniques similar to those employed in assessments of human cannabis users. In addition to informing medical and public policy decision making, findings from this project will lay the groundwork for a broader research program directed toward understanding the mechanisms by which developmental cannabis smoke exposure affects the brain and behavior.

描述（由申请人提供）：人类长期使用大麻与一系列情感、认知和神经改变有关，包括抑郁和焦虑的发生率较高，记忆和执行功能的缺陷，以及脑容量和白质完整性的区域性减少。新出现的证据表明，当幼年开始使用大麻时，这些变化更大，并且可以持续到戒断，这表明青少年接触大麻可能对发育中的大脑产生特别有害的影响。这些发现与啮齿动物模型的研究结果一致，这些研究表明，在青春期服用四氢大麻酚或其他大麻素激动剂会导致认知缺陷，并在成年后增加负面影响。然而，值得注意的是，几乎没有关于青少年接触大麻烟雾对神经行为结果影响的研究。这类研究的缺乏令人震惊，不仅因为吸烟是人类使用大麻的首选途径，而且因为大麻烟雾除了含有四氢大麻酚外还含有大量大麻素和其他化合物，其中一些已知具有精神活性，可能对大脑和行为产生持久影响。因此，为了评估大麻使用的因果影响，至关重要的是采用一种模拟人类实际接触条件的模型。这项研究计划的长期目标是确定青少年接触大麻烟雾如何影响成人的情感、认知和大脑结构/功能测量，这些测量显示在人类大麻使用者中发生了改变。对于实现这一长期目标至关重要的是，我们在大鼠身上建立了大麻烟雾暴露模型，该模型产生的血液中四氢大麻酚水平与人类相当，并且我们在长期暴露后证明了大麻依赖性。基于这些初步数据，以及关于大麻使用者的已发表文献，我们的中心假设是，青少年吸食大麻会对成年后的情绪和认知处理产生有害影响，并伴有相关脑回路的结构异常。我们将在大鼠模型中验证这一中心假设：1)确定青少年大麻烟雾暴露是否会影响成年期的负面影响（抑郁和焦虑样行为的测量）；2)确定青少年大麻烟雾暴露是否影响成年期的多项记忆和执行功能；3)使用类似于评估人类大麻使用者的神经成像技术，确定青少年大麻烟雾暴露是否会影响成年期的脑容量和白质完整性。除了为医疗和公共政策决策提供信息外，该项目的研究结果还将为一个更广泛的研究项目奠定基础，该研究项目旨在了解发育过程中吸食大麻对大脑和行为的影响机制。