Teratogenic Effects of Marijuana in Developing Chick CNS

描述(由申请人提供)：该提案的目标是评估大麻对发育中的神经系统的致畸作用。大麻是孕妇最常使用的违禁药物。其主要精神活性成分THC通过胎盘积聚在胎儿大脑中，潜在损害中枢神经系统的发育，怀孕早期使用大麻与流产和后代10岁时的认知异常有关，如智商低下和学习障碍、记忆障碍和ADHD。动物模型显示，在相当于人类怀孕2-3周的时间内接触THC会导致发育中的神经系统畸形。在这个时间点上，大多数女性并不知道自己怀孕了，因此也不知道大麻的潜在有害影响。我们建议使用显微外科、药理学和分子生物学相结合的方法，以鸡为动物模型，来表征大麻对大脑发育初始阶段的胚胎毒性效应。这项研究将为更好地了解怀孕早期接触大麻的风险提供信息，并将作为涉及酒精、可卡因、甲苯丙胺和鸦片类药物或其组合等其他滥用药物的致畸研究的基础。

DESCRIPTION (provided by applicant): The goal of the proposal is to assess the teratogenic effects of marijuana on the developing nervous system. Marijuana is the most commonly used illicit drug by pregnant women. Its major psychoactive constituent, THC, crosses the placenta and accumulates in fetal brain, potentially harming CNS development, marijuana use in early pregnancy is associated with miscarriage and cognitive abnormalities at age 10 in the offspring, such as lower IQ and learning disabilities, memory impairment and ADHD. Animal models show that THC exposure at a period corresponding to weeks two-three of human pregnancy, results in teratogenesis of the developing nervous system. At this time point, most women are unaware of their pregnancy, and thus of the potentially harmful effects of marijuana. We propose to use a combination of microsurgical, pharmacological and molecular approaches using chick as an animal model, to characterize the embryotoxic effects of marijuana on the initial steps of brain development. This research will provide information for a better understanding of the risks of marijuana exposure during early pregnancy, and will serve as a basis for teratogenic studies involving other drugs of abuse, such as alcohol, cocaine, metamphetamine and opiates, or combinations thereof.