Dopamine terminal regions interact as a function of motivation and reinforcement

多巴胺末端区域作为动机和强化的函数相互作用

• 批准号: 7673119
• 负责人: Justin M Moscarello
• 金额: $ 3.16万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7673119
• 关键词: Address; Animals; Area; Behavior; Behavior Disorders; Behavioral; Behavioral Assay; Brain; Brain region; Cells; Chemicals; Data; Dopamine; Dopamine D2 Receptor; Dopamine Receptor; Drug Addiction; Drug abuse; FOS gene; Food; Food deprivation (experimental); Glutamates; Goals; Human; Literature; Medial; Mediator of activation protein; Microdialysis; Monitor; Motivation; Nervous system structure; Neurobiology; Neurons; Nucleus Accumbens; Organism; Output; Performance; Pharmaceutical Preparations; Prefrontal Cortex; Process; Proteins; Psychological reinforcement; Public Health; Research; Structure; Testing; Ventral Tegmental Area; Work; addiction; approach behavior; base; dopamine system; immunocytochemistry; in vivo; indexing; motivated behavior; neurochemistry; reinforcer; research study

DESCRIPTION (provided by applicant): A large body of evidence implicates the mesocroticolimbic dopamine (DA) system, specifically the medial prefrontal cortex (mPFC) and nucleus accumbens (NAcc) in the neurobiology of natural (e.g. food) and artificial (e.g.drug) reinforcement, as well as motivational states associated with goal-seeking. However, relatively little has been established about how these two brain regions interact as a function of alterations in motivational state or reinforcer magnitude, or how such interactions modify the output of goal-direceted behavior. The current proposal is therefore intended to better understand the functional relationship between the mPFC and NAcc as it relates motivated behavior. The project has three specific aims. First, to build upon preliminary data obtained with c-Fos (a protein marker of neuronal activation) by employing in vivo microdialysis to further understand the interaction between mPFC and NAcc as a function of manipulations of motivational state and reinforcer magnitude. Second, to assess the effects of chemical inhibition and excitation of both mPFC and NAcc as it pertains to multiple behavioral indices of motivation (i.e. progressive ratio reponding for food reinforcement; conditioned approach behavior in an operant runway). Third, to assess the effects of D1/D2 antagonism in both mPFC and NAcc with respect to performance in the same behavioral assays. Understanding of the functional relationship between mPFC and NAcc as it pertains to motivation will provide crucial evidence about the processes by which the nervous system serves to organize behavior. Ample research in humans and in animals suggests that the brain regions under study in this proposal are crucial mediators of addiction, as well as other behavioral disorders with a motivational component. Thus, a complete understanding of how these brain areas function is necessary in order to fully address a number of important issues of public health.

描述（由申请人提供）：大量证据表明中脑皮质多巴胺（DA）系统，特别是内侧前额叶皮层（mPFC）和伏隔核（NAcc）在自然（如食物）和人工（如药物）强化的神经生物学中，以及与目标寻求相关的动机状态中起作用。然而，关于这两个大脑区域如何作为动机状态或强化物大小改变的功能相互作用，或者这种相互作用如何改变目标导向行为的输出，人们的研究相对较少。因此，目前的建议是为了更好地理解mPFC和NAcc之间的功能关系，因为它涉及动机行为。该项目有三个具体目标。首先，基于体内微透析获得的c-Fos（神经元激活的蛋白质标记物）的初步数据，进一步了解mPFC和NAcc之间的相互作用作为动机状态和强化物大小操纵的函数。其次，评估mPFC和NAcc的化学抑制和激发作用，因为它与动机的多个行为指标（即食物强化的递进比反应；操作性跑道的条件趋近行为）有关。第三，在相同的行为分析中，评估mPFC和NAcc中D1/D2拮抗剂对表现的影响。了解mPFC和NAcc在动机方面的功能关系，将为神经系统组织行为的过程提供重要证据。在人类和动物身上进行的大量研究表明，该提议所研究的大脑区域是成瘾以及其他带有动机成分的行为障碍的关键媒介。因此，全面了解这些大脑区域的功能是必要的，以便充分解决一些重要的公共卫生问题。