PRENATAL COCAINE AND BRAIN DEVELOPMENT

产前可卡因与大脑发育

基本信息

批准号：
2121357
负责人：
ABIGAIL M SNYDER-KELLER
金额：
$ 10.06万
依托单位：
WADSWORTH CENTER
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-08-01 至 1999-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2121357
关键词：
basal ganglia behavioral habituation /sensitization cocaine convulsions developmental neurobiology dopamine dosage embryo /fetus toxicology fos protein immunocytochemistry laboratory rat limbic system prenatal stress regulatory gene serotonin

项目摘要

The long-term consequences of prenatal exposure to cocaine remains a major public health concern. The presence of cocaine during critical periods of brain development could result in permanent changes in animals are necessary to answer two basic questions: 1) Do alternations in neural development resulting from prenatal cocaine exposure produce permanent changes in the structure of the brain? and (2) Does exposure to cocaine alter the neural and behavioral effects of cocaine later in life? These questions will be addressed by a combination of anatomical and behavioral analyses. The studies proposed here will focus on regions of the basal ganglia and limbic system that are most affected by cocaine's stimulant and epileptogenic actions. The experiments in section I will determine whether alterations in the distribution and density of dopaminergic and serotonergic afferents to the stratum, nucleus accumbens, cortex, hippocampus and amygdala occurs in prenatally cocaine-treated rats. The second set of experiments will examine differences in the behavioral and neural response to cocaine later in life, as a function of prenatal cocaine exposure. First, the ability of prenatally cocaine-treated rats to tolerate cocaine in adulthood will be examined by assessing seizure incidence after exposure to acute high doses or chronic lower doses of cocaine. These experiments will provide a behavioral index for assessing a greater sensitivity to the toxic effects of cocaine as a result of prenatal exposure. Next, we will examine induction of the immediate- early gene c-fos after re-exposure to cocaine later in life. Cells exhibiting increases in the Fos protein in response to cocaine or cocaine-induced seizures will be mapped using immunocytochemical techniques, and compared to the distribution of Fos-immunoreactive cells in normal animals. Correlations between regional anatomical alterations and changes in sensitivity to cocaine-induced seizures will be sought. In addition, we will vary the dose and timing of cocaine administration during development, in order to determine the critical period for the changes observed. These studies will help determine how early exposure to cocaine alters brain development in ways that affect later functioning.

产前接触可卡因的长期后果仍然是一个主要公共卫生问题。关键时期存在可卡因大脑发育时期可能会导致动物发生永久性变化有必要回答两个基本问题：1）进行交替产前接触可卡因导致的神经发育大脑结构的永久性变化？ (2) 是否暴露可卡因稍后会改变可卡因的神经和行为影响生活？这些问题将通过解剖学的结合来解决和行为分析。这里提出的研究将重点关注基底神经节区域和边缘系统受可卡因兴奋剂影响最大致癫痫作用。第一节中的实验将确定多巴胺能和密度的分布和密度是否改变血清素能传入层、伏隔核、皮质，海马体和杏仁核出现在产前接受可卡因治疗的大鼠中。这第二组实验将检查行为和行为方面的差异晚年对可卡因的神经反应，作为产前的函数可卡因暴露。一、产前可卡因治疗大鼠的能力通过评估癫痫发作来检查成年后对可卡因的耐受性暴露于急性高剂量或慢性低剂量后的发病率可卡因。这些实验将为评估提供行为指标由于以下原因对可卡因的毒性作用更加敏感产前暴露。接下来，我们将检查立即的归纳晚年再次接触可卡因后的早期基因 c-fos。细胞对可卡因或可卡因的反应表现出 Fos 蛋白的增加可卡因诱发的癫痫发作将使用免疫细胞化学进行绘制技术，并与 Fos 免疫反应细胞的分布进行比较在正常动物中。区域解剖学改变之间的相关性将寻求对可卡因引起的癫痫发作的敏感性的变化。此外，我们将改变可卡因给药的剂量和时间在发展过程中，确定关键时期观察到的变化。这些研究将有助于确定早期暴露如何可卡因会以影响以后的方式改变大脑发育发挥作用。