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主要的公共卫生问题。临界期间可卡因的存在大脑发育时期可能导致动物永久变化回答两个基本问题是必要的：1）在产前可卡因暴露产生的神经发育产生大脑结构的永久变化？（2）确实接触可卡因改变可卡因后来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介绍基底神经节和边缘系统受可卡因兴奋剂和最大影响的边缘系统癫痫发作。我将确定的实验多巴胺能和密度的变化和多巴胺能和密度是否改变血清素能传入层，伏隔核，皮质，皮质，海马和杏仁核发生在产前可卡因治疗的大鼠中。这第二组实验将检查行为和行为的差异神经对可卡因后期对可卡因的反应，作为产前的功能可卡因暴露。首先，产前可卡因治疗的大鼠的能力在成年中忍受可卡因，将通过评估癫痫发作来检查暴露于急性高剂量或慢性较低剂量后的发生率可卡因。这些实验将为评估的行为指数提供由于产前暴露。接下来，我们将研究直接的诱导生命后期重新接触可卡因后，早期基因C-fos。细胞响应可卡因或可卡因诱导的癫痫发作将使用免疫细胞化学绘制技术，并与FOS免疫反应细胞的分布进行了比较在普通动物中。区域解剖变化之间的相关性将寻求对可卡因诱导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开发过程中，为了确定观察到的变化。这些研究将有助于确定如何早期暴露可卡因以影响以后的方式改变大脑的发育功能。