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

摘要 含有Δ9-四氢大麻酚(THC)的食品，THC是由 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 对青少年发育中的大脑急需使用。Stella和Stella之间令人兴奋的合作 陆地实验室开发并验证了一种新的模型来研究THC的口腔自我给药 会影响青春期啮齿动物的大脑，并导致成年后的行为障碍。因此，这种自愿的模式 口服THC-明胶食品达到相应的血液THC水平，产生急性大麻仿制品 这种药物有很好的药效，很容易与其他药物结合使用，这里指的是大麻二酚(CBD)。 青春期是神经系统仍在成熟的关键时期，尤其是在 边缘系统，而药物使用破坏这种成熟可能会导致严重的行为障碍 成人期。我们的初步结果突出了货柜码头处理机首批成功的自我管理模式之一。 啮齿动物，从而能够比较自愿THC对大脑发育的长期后果 和行为结果。 我们的新问题是确定青少年长期单独或联合使用THC的情况 CBD影响1)拟大麻反应，这可能为2)改变的机制提供洞察力 中皮质边缘系统内的信号，这可能决定成人动机行为和 对阿片类药物的疼痛反应。我们的目标是确定： 目的1：建立青春期小鼠THC-THC/CBD最佳摄取方案。 目的2：青春期摄入THC和THC/CBD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一种创新的小鼠自愿口服模型，将 提高我们对THC和THC/CBD使用对青少年大脑影响的机械性理解 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.