PEPTIDE MODULATION OF MESOLIMBIC DOPAMINE: BEHAVIORAL A

中脑边缘多巴胺的肽调节：行为 A

• 批准号: 3461087
• 负责人: Ann E. Kelley
• 金额: $ 6.84万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-01 至 1993-05-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3461087
• 关键词: auditory discrimination; behavior; brain mapping; chemical stimulation; computer data analysis; dopamine; dopamine receptor; drug interactions; dynorphins; endogenous opioid; enkephalins; laboratory rat; limbic system; microinjections; neuroanatomy; neuropharmacology; neurotensin; peptide analog; perception; prosencephalon; psychological reinforcement; psychomotor function; reinforcer; sensory discrimination; stereotaxic techniques; substance P; tegmentum

The mesolimbic dopamine (DA) system, which originates in the ventral tegmental area (VTA) and projects to limbic forebrain regions, plays a crucial role in mediating several important aspects of behavior. Mesolimbic DA neurons have been shown to be involved in such diverse functions as facilitation of motor output, reinforcement (including mediation of the rewarding properties of drugs of abuse), sensory and attentional processes. Surrounding these DA neurons are multiple networks of neuropeptide-containing nerve fibers, such as those containing opioid peptides, tachykinins, and neurotensin. Biochemical and behavioral experiments have suggested that these peptides have an important modulatory influence on the activity of mesolimbic DA neurons. Given the multiplicity of functions ascribed to the DA neurons and the striking diversity of peptidergic innervation associated with them, it would seem likely that their differential peptidergic modulation may constitute the substrate of different behavioral processes. The major objective of this project is to determine what specific behavioral processes these peptide-DA interactions are mediating. To accomplish this goal, paradigms which are able to distinguish drug effects on reinforcement, motor and sensory processes will be integrated with central microinfusion of putative peptide neurotransmitters. This will enable anatomically and chemically specific manipulations of VTA neuronal subpopulations, and evaluation of the behavioral state induced by the peptides. This investigation has direct relevance to the problem of drug abuse, which is a major medical and social problem. Of particular concern at the present moment are stimulant drugs such as cocaine and amphetamine, as well as opiate substances. There is convincing evidence that these two classes of drugs act on the mesolimbic dopamine system to produce a highly reinforcing behavioral state. Thus further study of the basic mechanisms of endogenous peptides which modulate this system may contribute to our understanding of how psychostimulant and opiate drugs produce their psychological effects, and may also help the development of new therapeutic treatment of drug addiction. Moreover, the proposed experiments specifically examine how peptide-dopamine interactions contribute to brain mechanisms of reward and motivation, which may further increase our knowledge of the reinforcing properties of self-administered drugs.

中脑边缘多巴胺（DA）系统，起源于 腹侧被盖区（VTA）和边缘前脑投射 在调解几个重要问题方面发挥着关键作用， 行为的方面。 已证明中脑边缘DA神经元 参与各种功能，如促进运动 产出，强化（包括奖励的调解 滥用药物的性质）、感觉和注意力过程。 围绕着这些DA神经元的是多个网络， 含有神经肽的神经纤维，例如含有 阿片肽、速激肽和神经降压素。 生化和 行为实验表明，这些肽 一个重要的调节影响的活动， DA神经元。 鉴于赋予联合国的多重职能， DA神经元和肽能神经支配的惊人多样性 与他们相关的，似乎他们的差异 肽能调节可能构成不同的底物 行为过程 该项目的主要目标是 确定这些肽DA 互动是中介。 为了实现这一目标， 能够区分药物对强化的影响， 运动和感觉过程将与中枢神经系统整合在一起， 微量输注推定的肽类神经递质。 这将 能够对腹侧被盖区进行解剖学和化学上的特异性操作 神经元亚群和行为状态的评价 由肽诱导。 这次调查与 药物滥用问题，这是一个重大的医疗和社会问题， 问题. 目前特别令人关切的是 可卡因和安非他明等兴奋剂，以及 鸦片类物质 有确凿的证据表明这两个 一类药物作用于中脑边缘多巴胺系统， 产生高度强化的行为状态。 因此，进一步研究 内源性肽的基本机制， 这个系统可能有助于我们理解 精神兴奋剂和阿片类药物产生他们的心理 效果，也可能有助于开发新的治疗方法。 戒毒治疗。 此外，拟议的实验 专门研究肽-多巴胺相互作用 有助于大脑的奖励和动机机制， 可以进一步增加我们对增强性能的了解 自我管理的药物。