REGULATION OF MESOLIMBIC DOPAMINE BY ENDOGENOUS COMPOUND

内源性化合物对中脑边缘多巴胺的调节

• 批准号: 3379242
• 负责人: Peter W Kalivas
• 金额: $ 10.77万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-01-01 至 1990-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3379242
• 关键词: amphetamines; chordate locomotion; cocaine; decarboxylase inhibitor; dihydroxyphenylalanine; disease /disorder model; dopamine; enkephalins; ethology; experimental brain lesion; gamma aminobutyrate; glutamate decarboxylase; immunochemistry; immunocytochemistry; laboratory rat; microinjections; microscopy; neuroanatomy; neurochemistry; neuropharmacology; neuropsychology; neurotensin; neurotransmitter metabolism; neurotransmitter receptor; neurotransmitters; nucleus accumbens; postmortem; psychomotor function; radioimmunoassay; schizophrenia; stereotaxic techniques; substantia innominata

A considerable research effort as been made to characterize the capacity of neurotransmitters to modulate the mesolimbic dopamine (DA) system, which has neuronal perikarya in the AlO region and axonal terminals in the nucleus accumbens (NA). Recently, it has become clear that efferent projections from the NA to the substantia innominata (SI) and from the SI to the pedunculopontine nucleus (PPN) play a major role in mediating the behavioral stimulant effect of increased mesolimbic DA activity. Because of its anatomical connections, the neuronal circuit from the AlO region - NA - SI - PPN - AlO region, the mesolimbic locomotor circuit (MLC), is thought to play a major role in integrating the limbic system with motor systems, thereby allowing motivation to be translated into adaptive motor behaviors. Four neurotransmitters have been identified as playing a major role in modulating MLC activity, including DA, gaminobutyric acid (GABA), enkephalin and neurotensin. In the present proposal these transmitters, or analogues, will be microinjected into the nuclei of the MLC, and changes measured in 1) spontaneous motor activity, 2) DA neurochemistry, 3) GABA neurochemistry, and 4) neurotensin and Met-enkephalin levels. Alternatively, the nuclei will be lesioned and changes evaluated. The neuroanatomy of transmitters within the MLC will be determined by using anterograde and retrograde tracing combined with immunocytochemistry, and by measuring the receptors of the transmitters using light microscopic receptor autoradiography. Finally, experiments are included to evaluate the role of the MLC in the psychostimulant model of psychosis. These studies are designed to determine the neuroanatomy, neurochemistry and function of the MLC, and to evaluate a role in the psychostimulant model of psychosis. This proposal constitutes a novel series of experiments that will expand our understanding of how the limbic system integrates with motor systems. Considering the proposed role for the MLC in the pathophysiology of psychosis, and the motor side-effects associated with current antipsychotic psychopharmacologic therapy, the information generated by these studies may impact our understanding and treatment of psychosis.

已经进行了相当大的研究工作来表征 神经递质调节中脑边缘多巴胺的能力 (DA)系统，其在AlO区域具有神经元胞体， 轴突终末位于延髓核（NA）。 近日更 很明显，从NA到 无名质（SI）和从SI到脚桥脑 核（PPN）在介导行为 增加中脑边缘DA活性的刺激作用。 因为 它的解剖学连接，神经回路， AlO区-NA-SI- PPN - AlO区，中脑边缘运动 电路（MLC），被认为是发挥主要作用， 边缘系统与运动系统，从而使动机， 转化为适应性运动行为。 四 神经递质已被确定为在 调节MLC活性，包括DA，γ-氨基丁酸（GABA）， 脑啡肽和神经降压素。 在本提案中， 神经递质或类似物将被显微注射到细胞核中 的MLC，以及在1）自发运动活动， 2)DA神经化学，3）GABA神经化学，和4）神经降压素 和甲硫氨酸脑啡肽水平。 或者，原子核将是 评估和改变。 递质的神经解剖学 将通过使用顺行和 逆行追踪结合免疫细胞化学， 用光学显微镜测量递质的受体 受体放射自显影 最后，包括实验， 评价MLC在精神兴奋剂模型中的作用， 精神病 这些研究旨在确定神经解剖学， MLC的神经化学和功能，并评估在 精神病的精神兴奋剂模型 这一提议构成 一系列新颖的实验将扩展我们对 大脑边缘系统如何与运动系统整合。 考虑到MLC在病理生理学中的拟定作用 精神病，以及与电流相关的运动副作用 抗精神病药物治疗，信息 这些研究可能会影响我们的理解， 精神病的治疗