Development of Rodent Self-Administration Vapor Inhalation Chambers for THC

 描述(由申请人提供)：这项SBIR第二阶段提案将加快开发步伐，并支持自行给药蒸汽吸入室系统的最终商业化，该系统用于向大鼠肺内递送大麻的主要精神活性成分∆9-四氢大麻酚(THC)。大麻仍然是美国使用的最受欢迎的非法精神活性药物。大约70%-80%的40-50岁的人一生中至少尝试过一次大麻，18-21岁的人中有18%-19%的人在过去的一个月里使用过大麻。在美国，符合大麻依赖标准的人比在过去一个月里使用可卡因或尝试海洛因的人更多。令人进一步关切的是，医用大麻法律规定的大麻使用量继续扩大。进一步从机制上了解THC依赖的发展和治疗方法的发现是一个越来越重要的目标，然而，由于大鼠无法通过传统的静脉途径自我给药，进展已经放缓。本项目的研究旨在进一步改进我们的仪器，以创建可靠的THC蒸汽吸入自我给药大鼠模型。具体目标1下的研究将评估THC的药代动力学分布以及肺内暴露对体温调节、运动活动、眩晕和止痛的影响，以确定必要的暴露参数。目标是在大范围的血浆THC水平下实现良好控制的暴露，范围从行为效应的阈值到可产生反复暴露的依赖的剂量。目标2下的研究将建立对THC的依赖以及使用挥发性THC作为增强剂的可操作的自我给药。AIM 3下的研究将测试特定的仪器 目标1和目标2以及研究战略中详述的初步数据所规定的设计更改。

 DESCRIPTION (provided by applicant): This SBIR Phase II proposal will enhance the pace of development and support the eventual commercialization of a self-administration vapor inhalation chamber system for the intrapulmonary delivery to rats of ∆9-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis. Cannabis remains the most popular illicit psychoactive drug used in the US. Some 70-80% of 40-50 year olds have tried cannabis at least once in their lifetime and 18-19% of 18-21 year olds have used cannabis in the past month. There are more people in the US who meet criteria for cannabis dependence than have used cocaine in the past month or ever tried heroin. It is of further concern that the use of cannabis under medical marijuana laws continues to expand. Further mechanistic understanding of how dependence of THC develops and the discovery of therapeutics is an increasingly critical goal, yet progress has been slowed by the failure of rats to readily self-administer THC by the traditional intravenous route. The studies in this project seek to further refine our instrumentation to create a reliable rat model of THC self-administration via vapor inhalation. Studies under Specific Aim 1 will assess the pharmacokinetic distribution of THC as well as effects of intrapulmonary exposure on thermoregulation, locomotor activity, catalepsy, and analgesia, to determine necessary exposure parameters. The goal is to achieve well-controlled exposure under a broad range of plasma THC levels which range from threshold of behavioral effects to doses which can produce dependence with repeated exposure. Studies under Aim 2 will establish dependence on THC as well as operant self-administration using delivery of volatilized THC as a reinforcer. Studies under Aim 3 will test specific instrumentation design changes dictated by Aims 1 and 2, as well as by the preliminary data detailed in the Research Strategy.