Pharmacokinetic and motivational properties of vaporized cannabis in mice

汽化大麻在小鼠体内的药代动力学和激励特性

• 批准号: 10569883
• 负责人: Kristen Marie Delevich
• 金额: $ 22.95万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10569883
• 关键词: Acute; Address; Adolescence; Adolescent; Adult; Age; Animal Model; Animals; Behavior; Behavioral; Biological; Biological Factors; Brain; Cannabinoids; Cannabis; Catheterization; Cells; Cognitive; Communities; Consumption; Cues; Data; Discrimination; Dose; Drug Addiction; Drug Delivery Systems; Drug Exposure; Drug Kinetics; Ensure; Ethanol Metabolism; Explosion; Exposure to; Female; Fentanyl; Flowers; Formulation; Funding; Funding Opportunities; Future; Genetic; Genome; Goals; Human; Inbreeding; Inhalation; Injections; Intake; Intraperitoneal Injections; Intravenous; Laboratories; Lead; Long-Term Effects; Lung; Measures; Methods; Modeling; Monitor; Motivation; Mouse Strains; Mus; National Institute of Drug Abuse; Nicotine; Pattern; Pharmaceutical Preparations; Physiological; Plants; Plasma; Population; Pre-Clinical Model; Preparation; Property; Rattus; Regimen; Reinforcement Schedule; Reproduction; Research Personnel; Rewards; Rodent; Rodent Model; Route; Self Administration; Smoke; Standardization; Study models; Testing; Tetrahydrocannabinol; Validation; addiction; alcohol and other drug; brain behavior; cannabimimetics; cell type; cost; design; emotional behavior; feasibility testing; fetal marijuana exposure; genetic manipulation; innovation; insight; interest; intravenous injection; male; marijuana legalization; marijuana use; marijuana user; mouse model; multidisciplinary; novel; pharmacokinetics and pharmacodynamics; pre-clinical; response; sex; synthetic cannabinoid; tool; vapor; vaporization

PROJECT SUMMARY The legalization of cannabis in several states across the US has increased the need to better understand its effects on the body, brain, and behavior. Rodent models are particularly valuable in this respect because they provide precise control over external variables and the rodent brain shows structural and functional homology with the human brain in regions relevant to drug dependence and emotional behavior. However, obstacles to establishing preclinical animal models that more closely resemble human patterns of cannabis use have limited our ability to study the biological consequences of real-world cannabis use and misuse. To address this critical barrier in the field, the McLaughlin Laboratory recently developed and validated a novel vapor inhalation model for delivering cannabis extracts in an experimenter-controlled or response-contingent manner in rats. Although this model has provided valuable opportunities for examining cannabis-seeking behavior, the relatively limited genetic toolkit available in rats has hindered the use of cell type- and circuit-specific approaches. Conversely, the cutting-edge genetic tools available in mice make them an attractive model for studying how cannabis use impacts various biological endpoints in the brain and periphery. To implement an ecologically valid mouse model of cannabis use, we must first establish optimal cannabis vapor dosing parameters across conditions of age, sex, and strain and determine the feasibility of self-administration in mice to ensure replicability for future studies. Thus, the objective of this R21 proposal is to establish this model of cannabis use in inbred and outbred strains of male and female mice during adolescence and adulthood. In Aim 1, we will use an experimenter-controlled cannabis vapor delivery approach to determine the pharmacokinetic and behavioral effects of cannabis vapor exposure in inbred (C57BL/6) and outbred (CD-1) mouse strains of both sexes during adolescence and adulthood. In Aim 2, we will use these dosing parameters to determine whether cannabis vapor supports stable cannabis-seeking behaviors in mice of both sexes, ages, and strains. Together, these aims employ a technically innovative approach and will establish vital working parameters that will afford rigorous characterization of the pharmacokinetic and cannabimimetic effects of acute exposure to vaporized cannabis. Funding this R21 proposal will be the first step in generating necessary pilot data in mice that will support many future collaborative proposals from our multidisciplinary group of investigators (McLaughlin, Delevich, and Hayashi). Moreover, it will provide a valuable starting point for others in the WSU community and beyond that are interested in employing cannabis vapor delivery approaches in mice.

项目摘要 美国多个州的大麻合法化增加了更好地了解其的需求 对身体，大脑和行为的影响。啮齿动物模型在这方面特别有价值，因为他们 提供对外部变量的精确控制，啮齿动物大脑显示结构和功能同源性 与毒品依赖和情感行为有关的地区的人脑。但是，障碍 建立更与大麻使用的人类模式的建立临床前动物模型有限 我们研究现实大麻使用和滥用的生物学后果的能力。解决这个关键 该领域的障碍，麦克劳林实验室最近开发并验证了一种新型的蒸气吸入模型 用于在大鼠中通过实验者控制或反应方式进行大麻提取物。虽然 该模型为研究大麻行为提供了宝贵的机会，这是相对有限的 大鼠可用的遗传工具包阻碍了细胞类型和电路特异性方法的使用。反过来， 小鼠可用的尖端遗传工具使它们成为研究大麻使用方式的有吸引力的模型 影响大脑和周围的各种生物终点。实现生态有效的鼠标 大麻使用模型，我们必须首先建立最佳的大麻蒸气剂量参数 年龄，性别和压力并确定小鼠自我给药的可行性，以确保对未来的复制性 研究。因此，该R21提案的目的是建立在近交和 在青春期和成年期间，雄性和雌性小鼠的杂交菌株。在AIM 1中，我们将使用 实验者控制的大麻蒸气输送方法来确定药代动力学和行为 两性男性的近交（C57BL/6）和近交（CD-1）小鼠菌株中大麻蒸气暴露的影响 在青春期和成年期。在AIM 2中，我们将使用这些给药参数来确定是否是否 大麻蒸气支持性别，年龄和菌株的小鼠中稳定的寻求大麻的行为。 这些目标共同采用技术创新的方法，并将建立重要的工作参数 将对急性暴露的药代动力学和大麻效应的严格表征 蒸发大麻。资助此R21提案将是在小鼠中生成必要的试点数据的第一步 这将支持我们多学科研究人员的许多未来合作提案 （McLaughlin，Delevich和Hayashi）。此外，它将为WSU中的其他人提供一个宝贵的起点 社区及以后有兴趣在小鼠中采用大麻蒸气输送方法。