PSYCHOPHARMACOLOGY OF DOPAMINE ONTOGENY

这个第一个奖项的申请概述了一系列细胞外 电生理研究旨在提供新的临床前研究 关于中脑的生理学和药理学的信息 发育过程中含有多巴胺(DA)的神经元。解剖学上， 含多巴胺神经元的生理、生化和药理学 在过去的几十年里得到了广泛的研究。这个 单次给药的电生理特征及神经药理学研究 已鉴定的成年哺乳动物多巴胺神经元已被许多人报道 调查人员。DA神经元经历快速而戏剧性的形态和 出生前和出生后个体发育过程中的功能变化尽管大多数 含有单胺的神经元和它们的轴突通路都很好 在出生时发育，许多突触发生在出生后 发展。人们对电生理学知之甚少 单一鉴定的哺乳动物多巴胺的特性和神经药理学 出生后发育期的神经元。实验是 在本申请内提出的，旨在澄清 的一些基本生理和药理特性 逆行鉴定DA神经元亚群。生理学和 逆行鉴定黑质纹状体(NSDA)的药理作用 将检查和比较中脑伏隔核(MADA)DA神经元 大鼠(1日龄至5周龄)的出生后发育 单单位胞外电生理技术。这个 发育中的NSDA和MADA神经元的生理特性 检查包括基本放电率、放电模式(例如，猝发 活动性)和传导速度。体细胞的出生后发育- NSDA和MADA神经元上的树突状和终末DA自身受体将是 使用系统和离子电泳法进行检查和比较 应用DA激动剂和拮抗剂。单胺类神经递质 已知在非常早期的产前出现在中枢神经系统 个体发育学。一些调查人员提出，单胺类化合物 神经递质，如多巴胺和5-羟色胺，可能具有营养作用 在发展中的中枢神经系统中的作用。这项提案中的实验是 旨在研究5-羟色胺能对产前和出生后的影响 NSDA的生理和药理研究进展 神经元。这些拟议的研究将提供有关 出生后的发育阶段，标志着向正常的发展 功能正常的成人DA神经元，这将与我们的理解相关 精神错乱症。

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.