Impact on adult mouse brain of oral THC and CBD consumption during adolescence

青春期口服 THC 和 CBD 对成年小鼠大脑的影响

• 批准号: 10206087
• 负责人: Nephi Stella
• 金额: $ 23.33万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10206087
• 关键词: 2-arachidonylglycerol; Acute; Adolescence; Adolescent; Adult; Affect; Applications Grants; Area; Behavior; Behavioral; Biological Markers; Blood; Brain; CNR1 gene; Cannabidiol; Cannabinoids; Cannabis; Collaborations; Consumption; Decision Making; Development; Down-Regulation; Drug Exposure; Drug Kinetics; Drug usage; Female; Gelatin; Glutamates; Impairment; Intake; Laboratories; Lead; Limbic System; Methods; Microscopy; Modeling; Molecular; Morphine; Motivation; Mus; Neurons; Nociception; Opioid; Oral; Outcome; Pain; Pattern; Pharmaceutical Preparations; Plants; Pre-Clinical Model; Predisposition; Publishing; Rattus; Regimen; Research; Resolution; Rewards; Rodent; Self Administration; Signal Transduction; Spinal Cord; Structure; System; Tetrahydrocannabinol; Time; United States; Ventral Tegmental Area; Vulnerable Populations; Work; adolescent brain development; adolescent drug abuse; adolescent drug use; behavioral impairment; behavioral outcome; behavioral response; brain tissue; cannabimimetics; cannabinoid receptor; conditioned place preference; critical period; gamma-Aminobutyric Acid; human model; innovation; insight; male; marijuana legalization; marijuana use; motivated behavior; mouse model; neurotransmission; novel; pain processing; painful neuropathy; phytocannabinoid; receptor expression; relating to nervous system; response; reward processing; sex; treatment response

Summary Edibles that contain Δ9-tetrahyrocannabinol (THC), the principal psychoactive ingredient produced by the cannabis plant, are becoming increasingly popular among adolescents, making examination of this method of use on the adolescent developing brain urgently needed. An exciting collaboration between the Stella and Land laboratories led to developing and validating a new model to study how oral self-administration of THC impacts adolescent rodent brain and ensuing behavioral impairment in adulthood. Thus, this model of voluntary oral consumption of THC-gelatin edibles achieves relevant blood THC levels, produces acute cannabimimetic effects and can easily be combined with other drugs, here cannabidiol (CBD). Adolescence is a critical period where maturation of neural systems is still occurring, particularly in the limbic system, and disruption of this maturation by drug use may lead to severe behavioral impairments in adulthood. Our preliminary results highlight one of the first successful self-administration models of THC in rodents, thereby enabling comparisons of the long-term consequences of voluntary THC on brain development and behavioral outcomes. Our new questions are to determine how long-term adolescent use of THC alone or in combination with CBD impacts 1) cannabimimetic response, which may provide insight as to the mechanism of 2) altered signaling within the mesocorticolimbic system, which may determine deficits in 3) adult motivated behavior and pain responses to opioids. Our aims are to determine: Aim 1: Establish optimal THC-THC/CBD consumption regimen by adolescent mice. Aim 2: Impact of THC and THC/CBD consumption during adolescence on adult mice behavioral responses to morphine. The completion of these studies, which utilize an innovative mouse model of voluntary oral consumption, will increase our mechanistic understanding of the impact of THC and THC/CBD use on adolescent brain development, and further determine how such perturbations influence motivated behavior and pain response to opioids.

概括 含有Δ9-四氢丙氨酸酚（THC）的食物，这是由主要的精神活性成分由 大麻植物在青少年中越来越受欢迎，对此方法进行了检查 在青少年发育中使用急需的大脑。斯特拉和斯特拉之间的激动人心的合作 土地实验室导致开发和验证一种新模型，以研究如何对THC进行口头自我管理 影响青少年啮齿动物的大脑并确保成年后的行为障碍。那，这种自愿模式 THC-明星蛋白食用的口服消耗达到相关的血液THC水平，产生急性大麻 效果，可以很容易地与其他药物合并，其中大麻二醇（CBD）。 青春期是仍在发生神经系统成熟的关键时期，尤其是在 边缘系统和通过吸毒对这种成熟的破坏可能导致严重的行为障碍 成年。我们的初步结果突出了THC的第一个成功自我管理模型之一 啮齿动物，从而可以比较自愿性交流对大脑发育的长期后果 和行为结果。 我们的新问题是确定单独使用THC或与之结合的长期青少年使用 CBD影响1）大麻响应，这可能提供有关机制2）改变的见解 中皮质降低系统内的信号传导，这可能决定在3）成人成熟行为和 对卵动物的疼痛反应。我们的目标是确定： AIM 1：通过青少年小鼠建立最佳的THC-THC/CBD消耗方案。 目标2：青少年期间THC和THC/CBD消耗对成年小鼠行为的影响 对吗啡的反应。 这些研究的完成，利用了自愿性口服消费的创新小鼠模型 增加我们对THC和THC/CBD对青少年大脑影响的机械理解 发展，并进一步确定这种扰动如何影响动机的行为和对 阿片类药物。