Cannabinoids in Early Sea Urchin Development

描述（由申请人提供）： 该项目符合NIDA/CEBRA标准，因为它提供了一种新的方法来评估早期妊娠期间暴露于药物滥用的潜在风险。该项目利用早期海胆胚胎作为模型系统，使用药理学扰动和救援策略。这种动物模型代表了一个敏感的，高通量的生物传感器系统筛选药物和神经毒物对早期胚胎发育的影响。 该项目调查了产前接触精神药物的影响，因为积累的证据表明，在神经系统出现之前，各种神经递质是海胆胚胎早期发育所必需的（“前神经递质”），并且有证据表明，这些功能是由类似于哺乳动物神经系统中发现的受体和载体介导的转运蛋白介导的。它专注于大麻素，因为1）以前的报道表明这些物质在受精和早期小鼠发育中发挥作用，2）初步证据表明大麻素，anandamide调节早期海胆发育，由CB 1受体和载体介导的转运蛋白介导。 具体目标旨在确定前神经大麻素系统的关键组成部分，包括受体和转运蛋白，并使用免疫化学和生物化学方法表征该系统的发育动力学。我们将确定大麻素引起的细胞表型变化，并寻找潜在的解毒剂来预防它们，包括新的亲脂性大麻素受体拮抗剂。预计这些研究将为潜在的治疗策略提供见解，以防止产前大麻素暴露的有害影响。未来的研究将在小鼠中测试这些治疗策略。

DESCRIPTION (provided by applicant): This project fulfills the NIDA/CEBRA criteria because it provides a novel approach to evaluate potential risks of exposure to drugs of abuse during early pregnancy. The project utilizes early sea urchin embryos as a model system, using a pharmacologic perturb-and-rescue strategy. This animal model represents a sensitive, high-throughput biosensor system for screening effects of drugs and neurotoxicants on early embryonic development. The project investigates effects of prenatal exposure to psychoactive drugs because of accumulated evidence that a variety of neurotransmitters are necessary for early development of sea urchin embryos, prior to the appearance of a nervous system ("pre-nervous neurotransmitters"), and evidence that these functions are mediated by receptors and carrier-mediated transporters similar to those found in the mammalian nervous system. It focuses on cannabinoids because of 1) previous reports that these substances play roles in fertilization and early mouse development, and 2) preliminary evidence that the cannabinoid, anandamide regulates early sea urchin development, mediated by CB1 receptors and carrier mediated transporters. The Specific Aims are designed to identify key components of the pre-nervous cannabinoid system, including receptors and transporters, and to characterize developmental dynamics of this system, using immunochemical and biochemical approaches. We will determine cell phenotype changes evoked by cannabinoids and search for potential antidotes to prevent them, including new lipophilic cannabinoid receptor antagonists. It is anticipated that these studies will provide insights into potential therapeutic strategies to prevent deleterious effects of prenatal cannabinoid exposure. Future studies will test these therapeutic strategies in the mouse.