PEPTIDE MODULATION OF MESOLIMBIC DOPAMINE: BEHAVIORAL A

中脑边缘多巴胺（DA）系统，起源于 腹侧被盖区 (VTA) 和投射到边缘前脑 地区，在调解几个重要问题方面发挥着至关重要的作用 行为方面。 中脑边缘 DA 神经元已被证明 参与诸如促进运动等多种功能 输出、强化（包括奖励的中介） 滥用药物的特性）、感觉和注意力过程。 围绕这些 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具有 对中脑边缘活动的重要调节影响 DA 神经元。 鉴于赋予的功能的多样性 DA 神经元和肽能神经支配的惊人多样性 与它们相关，它们的差异似乎很可能 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有哪些具体的行为过程 互动是中介。 为了实现这一目标，范式 能够区分药物对强化的影响， 运动和感觉过程将与中枢集成 推定的肽神经递质的微量输注。 这将 实现 VTA 的解剖学和化学特异性操作 神经元亚群和行为状态评估 由肽诱导。 这项调查具有直接相关性 药物滥用问题是一个重大的医学和社会问题 问题。 目前特别值得关注的是 可卡因和安非他明等兴奋剂以及 阿片类物质。 有令人信服的证据表明这两 作用于中脑边缘多巴胺系统的药物类别 产生高度强化的行为状态。 从而进一步研究 内源性肽调节的基本机制 这个系统可能有助于我们理解如何 精神兴奋剂和阿片类药物会产生心理作用 效果，也可能有助于新疗法的开发 治疗毒瘾。 此外，所提出的实验 特别检查肽-多巴胺如何相互作用 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 自行给药的药物。

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.