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

基本信息

批准号：
10039866
负责人：
Nephi Stella
金额：
$ 19.44万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-15 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10039866
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

项目摘要

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 Δ9-四氢大麻酚 (THC) 的食品，THC 是由大麻产生的主要精神活性成分大麻植物在青少年中越来越受欢迎，因此对这种方法进行了检查迫切需要将其用于青少年发育中的大脑。陆地实验室开发并验证了一种新模型，用于研究 THC 的口服自我给药方式影响青少年啮齿动物的大脑并随之而来的成年期行为障碍。口服 THC 明胶食品达到相关血液 THC 水平，产生急性大麻模拟物效果并且可以很容易地与其他药物结合使用，这里是大麻二酚（CBD）。青春期是神经系统仍在成熟的关键时期，特别是在边缘系统，而药物使用对这种成熟的破坏可能会导致严重的行为障碍我们的初步结果凸显了 THC 的第一个成功的自我管理模式之一。啮齿类动物，从而能够比较自愿 THC 对大脑发育的长期影响和行为结果。我们的新问题是确定青少年单独使用 THC 或与 THC 结合使用的长期程度如何？ CBD 影响 1) 大麻模拟反应，这可能有助于了解 2) 改变的机制中皮质边缘系统内的信号传导，可能决定 3) 成人动机行为和对阿片类药物的疼痛反应我们的目标是确定：目标 1：建立青春期小鼠的最佳 THC-THC/CBD 消耗方案。目标 2：青春期 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口服消费的创新小鼠模型，将增加我们对 THC 和 THC/CBD 使用对青少年大脑影响的机制理解发展，并进一步确定这些扰动如何影响动机行为和疼痛反应阿片类药物。