Prenatal Cannabis Effect on the Endocannabinoid System

描述（由申请人提供）：大麻是许多国家最广泛滥用的药物之一，长期以来一直被认为是一种对运动和认知功能有广泛影响的中枢作用药物。尽管它是育龄妇女中滥用最广泛的药物，但关于其对后代的神经化学和神经行为后果，特别是长期影响的文献相对较少。中枢神经系统中的内源性大麻素与调节腺苷酸环化酶、离子通道和细胞外信号调节激酶的G蛋白偶联CB 1受体结合。已知内源性大麻素系统在健康和疾病的许多方面发挥重要作用，包括药物成瘾。由于δ-9四氢大麻酚（？9-THC）是大麻的主要精神活性成分和CB 1受体的部分激动剂，据推测，在子宫内？9-THC暴露改变了内源性大麻素系统和CB 1受体介导的信号通路的功能。在拟议的研究中，我们将探讨产前？9-以C57 BL/6 J小鼠为动物模型，研究了THC暴露对仔鼠脑内源性大麻素系统的影响。拟议的研究是及时的，这项研究的结果将具有很大的潜力，为开发药物治疗干预产前大麻相关的出生缺陷。在滥用的药物中，产前滥用大麻已成为一个主要的公共健康问题。本研究的长期目标是了解子宫内THC暴露对发育中的CNS的细胞和分子机制，并检查内源性大麻素系统作为治疗与产前大麻滥用相关的行为缺陷的潜在治疗靶点的可能效用。

DESCRIPTION (provided by applicant): Cannabis sativa (Marijuana) is one of the most widely abused drugs in many countries and has long been recognized as a centrally acting drug with extensive effects on motor and cognitive functions. In spite of being the most widely abused drug among women of reproductive age, there is a relative paucity of literature dealing with the neurochemical and neurobehavioral consequences in offspring particularly the longer-term effects. The endocannabinoids in the central nervous system bind to G-protein coupled CB1 receptors that modulate adenylyl cyclase, ion channels and extracellular signal-regulated kinases. The endocannabinoid system is known to play an important role in many aspects of health and disease including drug addiction. Since delta-9 tetrahydrocannabinol (?9-THC) is a major psychoactive component of the marijuana and partial agonist of CB1 receptor, it is hypothesized that the in utero ?9-THC exposure alters the function of endocannabinoid system and CB1 receptor-mediated signaling pathway. In the proposed study, we will investigate the effect of prenatal ?9-THC exposure on the status of endocannabinoids system in the brain of offspring during postnatal development using C57BL/6J mice as an animal model. The proposed study is timely and the findings of this study would be of great potential for developing drug therapies in the intervention of prenatal cannabis related birth defects. Among drugs of abuse, prenatal cannabis abuse has become a major public health concern. The long- term goal of this study is to understand the cellular and molecular mechanisms of in utero THC exposure on the developing CNS and to examine possible utility of the endocannabinoid system as potential therapeutic target for the treatment of behavioral deficits associated with prenatal cannabis abuse.