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

总结 含有Δ9-四氢大麻酚（THC）的食品，THC是大麻生产的主要精神活性成分。 大麻植物，在青少年中越来越受欢迎，研究这种方法， 青少年大脑发育急需使用。Stella与 土地实验室导致开发和验证一种新的模型，以研究THC的口服自我管理 影响青春期啮齿类动物的大脑，并导致成年后的行为障碍。因此，这种自愿的模式 口服THC-明胶可食用物达到相关的血液THC水平，产生急性拟大麻素， 效果，可以很容易地与其他药物，这里大麻二酚（CBD）。 青春期是一个关键时期，神经系统的成熟仍在发生，特别是在 边缘系统，而药物使用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的第一个成功的自我管理模型之一， 啮齿动物，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长期单独使用THC或与THC联合使用 CBD影响1）大麻模拟反应，这可能提供关于2）改变的机制的见解。 中皮质边缘系统内的信号传导，这可能决定3）成人动机行为的缺陷， 阿片类药物引起的疼痛反应我们的目标是确定： 目的1：建立青春期小鼠最佳THC-THC/CBD消耗方案。 目的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 这些研究利用了一种自愿口服的创新小鼠模型， 增加我们对THC和THC/CBD使用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行为和疼痛反应， 阿片类药物。

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.