PRENATAL COCAINE EXPOSURE AND SEIZURE SUSCEPTIBILITY

产前接触可卡因的后果越来越令人担忧， 一个公共健康问题。 使用一个良好建立的动物模型， 在兔中的产前可卡因暴露（3 mg/kg可卡因IV，b.i.d.从 妊娠第8天（G8）至G29），我们将研究癫痫发作 后代对静脉注射可卡因的敏感性 局 这种模式的优点是我们可以轻松地 可以进行IV给药，这更类似于 人可卡因使用的常见模式的药代动力学，而不是IP或SC 模型 由于我们已经使用该模型收集了大量数据， 这证明了大脑中的分子和神经解剖学改变， GABA能系统作为产前可卡因暴露的结果，我们将 研究GABA能系统的功能是否改变， 与其相关的回应。 为此，我们将测量 后代对GABA受体的癫痫易感性 拮抗剂荷包牡丹碱。 另外，我们会比较- 可卡因和荷包牡丹碱的相关影响，以确定这些行为是否 都是通过共同的输出途径产生的。 我们将尝试 用蝇蕈醇预防可卡因引起的癫痫发作， GABA受体激动剂。 我们将研究的时间过程中， 对可卡因和荷包牡丹碱的耐受性 我们将确定是否有任何程度的交叉， 他们之间的宽容。 结果将提供有关 产前服用可卡因后GABA能系统功能障碍的程度 暴露，并将是潜在的有用的，在评估的影响， 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.