PSYCHOPHARMACOLOGY OF DOPAMINE ONTOGENY

这一首次获奖申请概述了一系列细胞外 电生理学研究旨在提供新的临床前 关于中脑的生理学和药理学的信息 多巴胺（DA）神经元在发育过程中。 解剖学， 含多巴胺神经元的生理、生化和药理学 在过去的几十年里被广泛研究。 的 神经电生理特性和神经药理学 许多人已经报道了鉴定出的成年哺乳动物DA神经元。 investigators. DA神经元经历快速和戏剧性的形态和 产前和产后个体发育过程中的功能变化。 虽然大多数 的单胺神经元和它们的轴突通路是良好的 在出生时发育，大部分突触发生在出生后 发展 人们对电生理学知之甚少， 单一哺乳动物DA的特征和神经药理学 出生后发育期的神经元。 实验 在本申请中提出的这些实施例旨在阐明 一些基本的生理和药理学特性， 逆向鉴定的DA神经元亚群。 生理和 逆向识别黑质纹状体（NSDA）的药理学， 将在实验期间检查和比较中脑（MADA）DA神经元。 大鼠（1日龄至5周龄）的产后发育， 单单位细胞外电生理技术。 的 发育中的NSDA和MADA神经元的生理特性， 检查的包括基础放电率，放电模式（例如，突发 活动）和传导速度。 体细胞的出生后发育- NSDA和MADA神经元中的树突状和末端DA自身受体将被 检查和比较使用系统和离子电渗 应用DA激动剂和拮抗剂。 单胺类神经递质是 已知出现在中枢神经系统在非常早期的产前 个体发育 许多研究人员提出，单胺 神经递质，如多巴胺和血清素，可能具有营养作用， 在发展中的CNS中发挥作用。 本提案中的实验是 旨在检查产前和产后的影响， NSDA生理和药理发育的传入 神经元 这些拟议中的研究将提供关于 出生后的发育阶段，标志着正常的进展， 功能正常的成年DA神经元，并将与我们的理解有关， 精神疾病的症状

This First Award application outlines a series of extracellular electrophysiological studies designed to provide new preclinical information concerning the physiology and pharmacology of mesencephalic dopamine (DA)-containing neurons during development. The anatomy, physiology, biochemistry and pharmacology of dopamine-containing neurons have been extensively studied over the past several decades. The electrophysiological characteristics and neuropharmacology of single identified adult mammalian DA neurons have been reported by many investigators. DA neurons undergo rapid and dramatic morphological and functional changes during prenatal and postnatal ontogeny. Although most of the monoamine-containing neurons and their axonal pathways are well developed at birth, much of the synaptogenesis occurs during postnatal development. Very little is known about the electrophysiological characteristics and neuropharmacology of single identified mammalian DA neurons during the postnatal developmental period. Experiments are proposed within this application which are directed towards elucidating some of the basic physiological and pharmacological properties of antidromically identified DA neuron subpopulations. The physiology and pharmacology of antidromically identified nigrostriatal (NSDA) and mesoaccumbens (MADA) DA neurons will be examined and compared during postnatal development in the rat (1-day-old to 5-weeks-old) using single-unit extracellular electrophysiological techniques. The physiological properties of developing NSDA and MADA neurons to be examined include basal discharge rate, discharge pattern (e.g., burst activity) and conduction velocity. The postnatal development of somato- dendritic and terminal DA autoreceptors in NSDA and MADA neurons will be examined and compared using both systemically and iontophoretically applied DA agonists and antagonists. Monoamine neurotransmitters are known to appear in the central nervous system during very early prenatal ontogeny. A number of investigators have proposed that monoamine neurotransmitters, such as dopamine and serotonin, may have trophic functions in the developing CNS. Experiments within this proposal are designed to examine the prenatal and postnatal influence of serotonergic afferents on the physiological and pharmacological development of NSDA neurons. These proposed studies will provide new critical data on the postnatal developmental stages which mark the progression to normally functioning adult DA neurons and will be relevant to our understanding of psychiatric disorders.