MATERNAL DRUG ABUSE: EFFECTS ON FETAL RAPHE DEVELOPMENT

妇女滥用可卡因和甲基苯丙胺的发生率 生育年龄的增长导致人口中虐待行为的增加 作为一个整体。 母体可卡因和/或METH对胎儿的影响 只有为数有限的几项研究探讨了虐待问题。 中 然而，这些研究中确定的行为缺陷是 表明脑干下部可能是毒品的作用部位. 由于延髓中缝核的细胞， 他们使用血清素（5-羟色胺; 5-HT）作为神经递质， 在包括睡眠在内的大量生理行为中发挥作用， 心血管、呼吸和体温调节，药物诱导的 5-羟色胺神经元可能有助于解释一些行为和生理 人类的异常 此外，由于长期服用可卡因和 甲羟色胺管理深刻影响血清素在成人，它可能很好地 也会影响发育中动物的血清素。 但他 这个大脑区域的药理学是复杂的， 延髓中缝内的肾上腺素能细胞也含有肽 神经递质P物质（SP）和促甲状腺激素释放激素（TRH）。 因此，我们建议检查母体可卡因和 通过检查对发育中的中缝核的影响， 发展色氨酸羟化酶（TPH）活性，5-HT水平，和co- 在整个胎儿发育过程中定位的肽类神经调节剂， 成年 由于进入发育中的哺乳动物中枢神经系统的途径有限， 然而，我们包括胚胎中缝的研究， 器官型组织培养，其中微环境的操纵是 更容易实现。 具体而言，我们会研究 中缝核生长在可卡因（或METH）的存在或不存在， 可能对TPH、5-HT、SP和TRH产生影响。

The incidence of cocaine and methamphetamine (METH) drug abuse among women of child-bearing age has paralleled the increase of abuse in the population as a whole. The consequences of the fetus of maternal cocaine and/or METH abuse have been addressed in only a limited number of studies. Among the behavioral deficits identified in those studies, however, are effects that point to the lower brainstem as a possible site of drug involvement. . Since cells of the raphe nuclei in the medulla oblongata, long defined by their use of serotonin (5-hydroxytryptamine; 5-HT) as a neurotransmitter, play a role in a vast array of physiological behaviors including sleep,, cardiovascular, respiratory, and thermo-regulation, drug-induced effects on 5-HT neurons may help explain some of the behavioral and physiological abnormalities described in humans. Moreover, since long-term cocaine and METH administration profoundly affect serotonin in the adult, it may well affect serotonin in the developing animal as well. However, he pharmacology of this brain region is complicated by the fact that serotonergic cells within the medullary raphe also contain peptide neurotransmitters substance P (SP) and thyrotropin-releasing hormone (TRH). We, therefore, propose to examine the effects of both maternal cocaine and METH administration on the developing raphe nuclei by examining effect on developing tryptophan hydroxylase (TPH) activity, 5-HT levels, and co- localized peptide neuromodulators throughout fetal development and into adulthood. Since access to the developing mammalian CNS is limited, however, we include the investigation of embryonic raphe maintained in organotypic tissue culture where manipulation of the microenvironment is more easily accomplished. Specifically, we will study the development of raphe nuclei grown in the presence or absence of cocaine (or METH) for possible consequences to TPH, 5-HT, SP, and TRH.