Prenatal Cannabis Effect on the Endocannabinoid System

产前大麻对内源性大麻素系统的影响

• 批准号: 7251849
• 负责人: VINOD K YARAGUDRI
• 金额: $ 18.7万
• 依托单位: NATHAN S. KLINE INSTITUTE FOR PSYCH RES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-25 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7251849
• 关键词: Prenatal; Cannabis; Effect; Endocannabinoid; System

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.

描述（由申请人提供）：大麻Sativa（大麻）是许多国家 /地区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产生广泛影响的中央表演药物。尽管在生殖年龄妇女中是最广泛滥用的药物，但在后代中涉及神经化学和神经行为的后代尤其是长期影响的文献相对匮乏。中枢神经系统中的内源性大麻素与G蛋白偶联的CB1受体结合，该受体调节腺苷环酶，离子通道和细胞外信号调节激酶。众所周知，内源性大麻素系统在包括药物成瘾在内的健康和疾病的许多方面都起着重要作用。由于Delta-9四氢大麻酚（？9-THC）是大麻的主要精神活性成分，并且是CB1受体的部分激动剂，因此假设子宫内的thc暴露会改变内源性大麻素系统和CB1受体受体介导的信号介导的信号介导的介导的功能。在拟议的研究中，我们将研究产前9-THC暴露对使用C57BL/6J小鼠作为动物模型的产后发育过程中后代大脑中内源性大麻素系统状态的影响。拟议的研究是及时的，这项研究的发现将在干预产前大麻相关的先天缺陷中开发药物疗法的巨大潜力。在滥用药物中，产前大麻滥用已成为一个主要的公共健康问题。这项研究的长期目标是了解开发中枢神经系统的子宫内THC暴露的细胞和分子机制，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标。