PRENATAL COCAINE EXPOSURE AND SEIZURE SUSCEPTIBILITY

产前接触可卡因的后果越来越令人担忧，因为 这是一个公共卫生问题。使用一种成熟的动物模型 家兔生前可卡因暴露(3 mg/kg可卡因静脉注射，b.i.d。从… 妊娠第8天(G8)至G29)，我们将对癫痫发作进行调查 子代对静脉注射可卡因的敏感性 行政管理。这种模式的优点是，我们可以轻松地 可以执行静脉给药，这更类似于 人体常见可卡因使用方式的药代动力学研究 模特们。由于我们已经使用此模型收集了大量数据 它们显示了分子和神经解剖学上的变化 GABA能系统作为产前可卡因暴露的结果，我们将 研究GABA能系统的功能是否在 关于其与癫痫有关的反应的条款。为此，我们将测量 子代对GABA受体反应的癫痫敏感性 拮抗剂荷包牡丹碱。此外，我们还会比较查获的- 可卡因和荷包牡丹碱的相关效应来确定这些行为 都是通过共同的输出途径产生的。我们将尝试 预防可卡因诱发癫痫的产生，一种 GABA受体激动剂。我们将研究时间进程， 可卡因和荷包牡丹碱诱导的耐受性研究进展 癫痫发作，我们将确定是否有任何程度的交叉- 他们之间的宽容。结果将是关于以下方面的信息 产前可卡因对GABA能系统功能障碍程度的影响 暴露，并将在评估影响潜在有用 抗惊厥药物。

The consequences of prenatal cocaine exposure are of growing concern as a public health issue. Using a well established animal model of prenatal cocaine exposure in rabbits (3 mg/kg cocaine IV, b.i.d. from gestation day 8 (G8) to G29), we will investigate the seizure susceptibility of the offspring in response to IV cocaine administration. The advantage of this model is the ease with which we can perform IV administration, which is more similar to the pharmacokinetics of common patterns of human cocaine use than IP or SC models. Since we have collected a large body of data using this model which demonstrate molecular and neuroanatomical alterations in the GABAergic system as a consequence of prenatal cocaine exposure, we will investigate whether the function of the GABAergic system is altered in terms of its seizure-related responses. To do so, we will measure the seizure susceptibility of the offspring in response to the GABA receptor antagonist bicuculline. In addition, we will compare the seizure- related effects cocaine and bicuculline to determine if these behaviors are produced through a common output pathway. We will attempt to prevent the production of cocaine-elicited seizures with muscimol, a GABA receptor agonist. We will examine the time course of the development of tolerance to both cocaine and bicuculline-elicited seizures, and we will determine whether there is any degree of cross- tolerance between them. Results will be informative concerning the degree of dysfunction of the GABAergic system following prenatal cocaine exposure and will be potentially useful in evaluating the effects of anticonvulsant medications.