THE DEVELOPMENTAL NEUROCHEMISTRY OF COCAINE

可卡因的发育神经化学

• 批准号: 3210424
• 负责人: Susan E. Robinson
• 金额: $ 16万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-30 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3210424
• 关键词: animal age group; cerebral cortex; cholinergic receptors; cocaine; corpus striatum; developmental neurobiology; dopamine receptor; drug administration rate /duration; drug administration routes; embryo /fetus toxicology; estrus; frontal lobe /cortex; gas chromatography mass spectrometry; high performance liquid chromatography; hippocampus; hypothalamus; intravenous drug abuse; laboratory rat; molecular psychobiology; neurons; neurotransmitter metabolism; norepinephrine; phosphorylcholine; prenatal growth disorder; serotonin receptor

The long-term goals of this work are to develop treatments for cocaine abuse, as well as for children with neurobehavioral abnormalities resulting from prenatal exposure to cocaine. Specifically, this project will (1) investigate the neurochemical and behavioral effects in rats of exposure to various doses of cocaine prenatally and (2) investigate the neurochemical and behavioral responses to intravenous cocaine in rats of varying ages and compare these responses to those of animals which have been exposed to cocaine in utero. It is postulated that prenatal exposure to cocaine can affect development of specific neurotransmitter pathways in the central nervous system. It is also postulated that animals of different ages may respond to cocaine in a different manner. Pregnant females will receive either intravenous injections of various doses of cocaine or saline or no treatment in pregnancy during prenatal development of dopaminergic, noradrenergic, and serotonergic neurons. The neurochemical effects of the above treatments will be studied in the neonate. Additional pups from these treatment groups will be fostered to surrogate dams. The neurochemistry and behavior of these pups will be studied both under control conditions and in response to cocaine in weanling (21 day) and sexually mature (60 day) rats. Male and female pups will be studied to determine if there are sex-related effects of prenatal cocaine exposure. Neurotransmitter content and neuronal activity will be estimated in specific brain regions for the following transmitters: acetylcholine (ACh), dopamine (DA), norepinephrine (NE) and serotonin (5-HT). Cholinergic neuronal activity will be assessed by quantitating ACh turnover by a mass fragmentographic technique that measures the relative incorporation of deuterium label from infused phosphorylcholine precursor into choline and ACh. The activity of DA, NE, and 5-HT neurons will be estimated by quantitating neurotransmitters and their metabolites using HPLC with electrochemical detection. Brain areas to be analyzed are frontal cortex, parietal cortex, hippocampus, striatum, hypothalamus, and medulla-pons. Behavioral testing will consist of measuring weight gain, simple reflexes, locomotor activity and habituation. Once the effect of exposure to cocaine either prenatally or postnatally on neurochemistry is more completely understood, then better treatment can be developed for cocaine abuse and for the neurobehavioral deficits exhibited by those exposed to cocaine prenatally.

这项工作的长期目标是开发可卡因的治疗方法。 虐待，以及导致神经行为异常的儿童 因为出生前接触了可卡因。具体地说，这个项目将(1) 研究染毒对大鼠神经化学和行为的影响 产前应用不同剂量可卡因及(2)神经化学研究 不同年龄和不同年龄大鼠对静脉注射可卡因的行为反应 将这些反应与暴露在空气中的动物的反应进行比较 子宫内的可卡因。据推测，产前接触可卡因可能会 影响中枢神经递质通路的发育 神经系统。还假设不同年龄的动物可能 以不同的方式对可卡因做出反应。怀孕的雌性将收到 无论是静脉注射不同剂量的可卡因或生理盐水 孕期多巴胺能神经发育的治疗， 去甲肾上腺素能和5-羟色胺能神经元。神经化学效应的研究 上述治疗方法将在新生儿身上进行研究。来自这些的更多幼崽 治疗组将被培育成替代大坝。神经化学和 这些幼崽的行为将在控制条件下和在 断奶(21天)和性成熟(60天)大鼠对可卡因的反应。 将对雄性和雌性幼崽进行研究，以确定是否存在与性有关的 产前可卡因暴露的影响。神经递质含量与神经元 将对以下特定大脑区域的活动进行估计 递质：乙酰胆碱(ACh)、多巴胺(DA)、去甲肾上腺素(NE)和 5-羟色胺(5-HT)。胆碱能神经元活性将通过以下方法评估 通过质量碎片图谱技术定量ACh周转 从输液中测量相对掺入的氚标记 磷酰胆碱前体转化为胆碱和乙酰胆碱。多巴胺、去甲肾上腺素、 5-羟色胺神经元将通过量化神经递质和 其代谢产物采用高效液相色谱-电化学法检测。脑区至 被分析的是额叶皮质、顶叶皮质、海马体、纹状体 下丘脑和延髓-桥脑。行为测试将包括 测量体重增加、简单反射、运动活动和习惯性。 一旦产前或产后接触可卡因对 对神经化学有了更全面的了解，才能得到更好的治疗 专为可卡因滥用和神经行为缺陷而开发 由那些产前接触可卡因的人造成的。