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（由适用提供）：人类中的慢性大麻使用与一系列情感，认知和神经改变有关，包括抑郁症和焦虑症的较高事件，定义记忆和执行功能，以及大脑体积和白质完整性的区域减少。新兴的证据表明，当大麻使用从很小的时候开始并且可以持续戒酒时，这些改变会更大，这表明青少年大麻暴露可能对发展中的大脑有特别删除的影响。这些发现与啮齿动物模型的研究一致，表明在青少年期间的9THC或其他大麻素激动剂的给药会导致认知缺陷，并在成年期间增加负面影响。但是，值得注意的是，几乎没有关于青少年暴露于大麻烟的影响对神经行为结局的影响。缺乏这样的研究令人震惊，这不仅是因为吸烟是人类大麻使用的首选途径，而且由于大麻烟雾含有许多大麻素和其他化合物，除了9THC，其中一些烟雾是精神活性的，并且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，使用模仿实际人类暴露状况的模型至关重要。该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人类大麻使用者改变的成人情绪，认知和大脑结构/功能措施。对这个长期目标很重要，我们已经在大鼠中建立了一种大麻烟雾暴露模型，该模型可产生与人类中发现的血液THC水平相当，并且我们在慢性暴露后证明了大麻依赖性。在这些初步数据以及有关大麻使用者的文献的基础上，我们的中心假设是，青少年大麻烟雾暴露会对成年期的情绪和认知处理产生有害影响，而这些情绪和认知处理是由相关脑电路中结构异常管理的。我们将通过以下大鼠模型中检验这一中心假设：1）确定青少年大麻烟雾暴露是否会影响成年期间的负面影响（抑郁症和动画行为）； 2）确定青少年大麻烟雾是否会影响成年后的多种记忆和执行功能； 3）确定青少年大麻烟雾暴露在成年期间是否会影响脑量和白质的完整性，使用类似于评估人类大麻使用者的神经成像技术。除了告知医疗和公共政策决策外，该项目的发现还将为一个更广泛的研究计划奠定基础，该计划致力于理解发展性大麻烟雾影响大脑和行为的机制。