NEURAL MECHANISMS IN THE NUCLEUS ACCUMENS AND BEHAVIOR

尖核的神经机制和行为

• 批准号: 2117307
• 负责人: Ann E. Kelley
• 金额: $ 15.75万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-01 至 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2117307
• 关键词: NMDA receptors; behavior; biological signal transduction; central nervous system stimulants; computer data analysis; dopamine; drug abuse; drug interactions; excitatory aminoacid; glutamates; inhibitor /antagonist; laboratory rat; limbic system; microinjections; neurochemistry; neuropharmacology; neurotransmitter metabolism; nucleus accumbens; opiate alkaloid; psychological reinforcement; reinforcer; stereotaxic techniques

It is estimated that there are presently over 2,000,000 regular drug users in this country. Two major classes of drugs, psychostimulants and opiates, comprise the majority of illicit substances used. Compulsive use and abuse of these drugs constitutes a major social and medical problem. The causes underlying drug abuse are complex, involving interactions of social, psychological and biological factors. The goal of neurobiological research is to understand how the brain is affected and changed by these compounds. Although many brain regions may be affected by drug use, particular focus has been given to the nucleus accumbens, a forebrain structure interposed between the limbic system and the motor system. Past research has shown that the nucleus accumbens mediates the reinforcing properties of both stimulants (cocaine and amphetamine) and opiates (heroin and morphine). The current proposal seeks to further examine neurotransmitter interactions and signal transduction mechanisms within the nucleus accumbens, using a behavioral-pharmacological approach in the rat. To accomplish this goal, direct brain microinjection of neurotransmitters or drugs will be employed in conjunction with behavioral paradigms that measure motor activity, responding for conditioned reward, and exploration. There are three major objectives of these experiments: 1) To investigate the role of glutamate-mediated corticolimbic input to the nucleus accumbens in the behavioral effects of psychostimulants and opiates. We will also study the role of glutamate in normal adaptive behavior subserved by the nucleus accumbens, such as exploration and spatial learning. 2) To investigate opiate-dopamine interactions in the nucleus accumbens, focusing particularly on the phenomenon of opiate-induced cross-sensitization to amphetamine and cocaine. 3) To study the role of specific signal transduction mechanisms in behavior mediated by the nucleus accumbens, and how manipulation of such systems may alter the behavioral response to psychostimulants and opiates. For these experiments, intra-accumbens microinjection of bacterial toxins that selectively interfere with G proteins will be carried out in conjunction with studies of motor activity and responding for conditioned reinforcement. Results from this project may contribute to advancement of knowledge in two domains: 1) More detailed understanding of both the behavioral and neurochemical changes induced by psychostimulants and opiates; 2) Further knowledge of the role of specific neural systems within the nucleus accumbens in behavior.

据估计，目前有200多万种常规药物， 用户在这个国家。 两大类药物，精神兴奋剂和 阿片剂占所用非法药物的大多数。 强迫性 这些药物的使用和滥用构成了重大的社会和医疗问题， 问题. 药物滥用的根本原因是复杂的， 社会、心理和生物因素的相互作用。 目标 神经生物学研究的重点是了解大脑是如何受到 并被这些化合物改变。 虽然许多大脑区域可能 受药物使用影响，特别关注核心 前脑，介于边缘系统和大脑皮层之间的前脑结构。 电机系统。 过去的研究表明， 介导两种兴奋剂（可卡因和 安非他明）和鸦片制剂（海洛因和吗啡）。 现时的建议 旨在进一步研究神经递质的相互作用和信号 转导机制内的核延髓，使用一个 行为药理学方法在大鼠。 为了实现这一目标， 直接脑内显微注射神经递质或药物将是 与测量运动的行为范式结合使用， 活动，对条件奖励的反应，以及探索。 有 这些实验的三个主要目标：1）研究作用 谷氨酸介导的皮质边缘输入到丘脑背核， 精神兴奋剂和阿片类药物的行为影响。 我们还将研究 谷氨酸在正常适应行为中的作用， 神经核，如探索和空间学习。2)到 研究脑桥核中阿片-多巴胺的相互作用， 特别侧重于阿片类药物引起的 对安非他明和可卡因交叉致敏。3)研究的作用 在行为中的特异性信号转导机制由 核神经元，以及如何操纵这些系统可能会改变 对精神兴奋剂和鸦片类药物的行为反应 为这些 实验中，微注射细菌毒素， 选择性干扰G蛋白将与 通过研究运动活动和对条件反射的反应， 加固. 该项目的结果可能有助于推进 在两个领域的知识：1）更详细的了解， 精神兴奋剂引起的行为和神经化学变化， 阿片类药物; 2）进一步了解特定神经系统的作用 在行为上是一致的。