DEVELOPMENTAL EFFECTS OF PRENATAL CANNABINOID EXPOSURE

描述（改编自研究者摘要）：本学术 研究促进奖（区域）的建议解决了产前的影响 暴露于δ-9-四氢大麻酚（THC）对神经内分泌和 免疫系统的发展和成年男性和女性后代。 尽管怀孕期间接触大麻已被证明会产生 对后代的长期神经内分泌影响，对 免疫系统尚未被研究。 在初步研究中， 大麻的主要精神活性成分，用于怀孕的老鼠 在怀孕的最后一周，已被证明会扰乱荷尔蒙 母亲和胎儿的环境。 因为发育中的免疫系统 胎儿的神经内分泌系统容易受到激素变化的影响， 在这个时候，暴露于THC的男性和女性后代可能 免疫和神经内分泌功能受损。 事实上，初步 研究结果支持这一假设，因为胸腺和脾脏重量 在发育过程中和成年雄性和雌性中显著改变 后代 此外，下丘脑神经递质含量，催乳素 水平和交配行为参数也受到影响， 在子宫内接触四氢大麻酚的后代 胸腺和脾脏的变化 体重是否反映了免疫功能的改变 是神经内分泌轴 （下丘脑-垂体-肾上腺和性腺）， 影响免疫系统的功能，由于暴露而受损 在中枢神经系统发育的关键阶段对四氢大麻酚的反应 在这项提案中， 申请人将通过以下方式检查这些问题：1）测量广泛的 THC的剂量范围（0.5-10 mg/kg）在产前给予免疫和 发育和成年后代的神经内分泌参数。 因为只有一个 将浓度为5 mg/kg的THC施用给初步大鼠 到目前为止，测试更宽剂量范围的影响将提供重要的 剂量反应数据，并允许在未来使用THC的最佳剂量 研究; 2）确定产前THC暴露对胎儿发育能力的影响。 T和B细胞对特定的有丝分裂原作出反应。 测量 丝裂原诱导的淋巴细胞增殖反应， 发育中和成年雄性和雌性后代的胸腺和脾脏将 传递关于基本免疫能力的重要信息; 3）检查 发育过程中和成年时胸腺和脾脏组织的组织学 在子宫内暴露于载体或THC的雄性和雌性后代; 4）确定 如果在子宫内暴露于THC会改变下丘脑-垂体-肾上腺和/或 - 雄性和雌性后代的性腺功能。 这些结果一起 将提供新的和急需的信息， THC宫内暴露对免疫和神经内分泌功能的影响 这反过来又将导致更好地了解产妇药物滥用 及其对雄性和雌性后代的影响。

DESCRIPTION (Adapted from the Investigator's Abstract): This Academic Research Enhancement Award (AREA) proposal addresses the effects of prenatal exposure to delta-9-tetrahydrocannabinol (THC) on the neuroendocrine and immune systems of the developing and adult male and female offspring. Although marijuana exposure during pregnancy has been shown to produce long-lasting neuroendocrine effects in the offspring, possible effects on the immune system have not been studied. In preliminary studies, THC, the major psychoactive component of marijuana, administered to pregnant rats during the last week of gestation, has been shown to disturb the hormonal milieu of mother and fetus. Because the developing immune and neuroendocrine systems of the fetus are vulnerable to changes in the hormone environment at this time, the male and female offspring exposed to THC may have compromised immune and neuroendocrine function. Indeed, preliminary findings support this hypothesis in that thymus and spleen weights were significantly altered during development and in adult male and female offspring. Moreover, hypothalamic neurotransmitter content, prolactin levels, and copulatory behavior parameters were also affected in the offspring exposed to THC in utero. Do the changes in thymus and spleen weight reflect alterations in immune function? Are the neuroendocrine axes (hypothalamic-pituitary-adrenal and -gonadal) that directly and indirectly affect the function of the immune system compromised as a result of exposure to THC during a critical stage of CNS development? In this proposal the applicant will examine these questions by 1) measuring the effects of a wide dose range of THC (0.5-10 mg/kg) administered prenatally on immune and neuroendocrine parameters of developing and adult offspring. As only one concentration of THC (5 mg/kg) has been administered to preliminary rats thus far, testing the effects of a wider dose range will provide important dose-response data and allow optimal doses of THC to be utilized in future studies; 2) Determine the effects of prenatal THC exposure on the ability of T and B cells to respond to specific mitogens. Measuring the mitogen-induced proliferation responses of Iymphocytes obtained from the thymus and spleen of developing and adult male and female offspring will impart important information concerning basic immunocompetence; 3) Examine the histology of thymus and spleen tissues during development and in adult male and female offspring exposed to vehicle or THC in utero; 4) Determine if in utero exposure to THC alters hypothalamic-pituitary-adrenal and/or -gonadal function of the male and female offspring. Together, these results will provide new and much-needed information concerning the potential effects of in utero THC exposure on immune and neuroendocrine function which, in turn, will lead to a better understanding of maternal drug abuse and its effects on male and female offspring.