Mesocorticolimbic Generation of Motivation

中皮质边缘的动机产生

• 批准号: 8267544
• 负责人: Jocelyn M Richard
• 金额: $ 1.96万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2012-11-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8267544
• 关键词: AMPA Receptors; Address; Amygdaloid structure; Appetitive Behavior; Behavior; Behavioral; DNQX; Disinhibition; Distress; Dopamine; Dopamine Antagonists; Dopamine D1 Receptor; Dopamine D2 Receptor; Dopamine Receptor; Drug Addiction; Environment; FOS gene; Feeding behaviors; Food; Fright; GABA Agonists; GABA Antagonists; Generations; Glutamates; Health; Health Care Costs; Hippocampus (Brain); Home environment; Human; Incentives; Injection of therapeutic agent; Measures; Medial; Mediating; Mental disorders; Microinjections; Motivation; Neurons; Nucleus Accumbens; Obesity; Paranoia; Pharmaceutical Preparations; Play; Prefrontal Cortex; Rattus; Recruitment Activity; Regulation; Relative (related person); Role; Schizophrenia; Signal Transduction; Site; Source; System; Testing; Thalamic structure; Therapeutic Intervention; cortico-limbic circuits; feeding; gamma-Aminobutyric Acid; immunoreactivity; mesolimbic system; motivated behavior; prevent; psychologic; research study; vocalization

PROJECT SUMMARY Aberrant motivation is an important feature of a variety of human mental disorders. Excessive appetitive motivation is implicated in drug addiction and obesity, leading to sometimes compulsive pursuit and overconsumption of drugs or food (1, 2). The nucleus accumbens (NAc), embedded within mesocorticolimbic circuits, plays an important role in excessive incentive motivation. The medial shell region of the NAc is particularly associated with the generation of appetitively motivated behaviors. Beyond the well known role in incentive motivation, mesocorticolimbic systems may also mediate some fearful states. This proposal focuses on the role of local glutamate disruptions in rostral NAc shell in producing positively-motivated behaviors like intense feeding, and the role of glutamate disruptions in caudal zones of NAc shell in producing negatively- motivated behaviors. Mesolimbic dopamine (DA) systems interact with corticolimbic glutamate disruptions for appetitive and fearful motivational salience (5): Aim 1 will identify whether D1 or D2 receptor subtypes are necessary for generation of either positively-motivated behaviors (feeding) in rostral shell or negatively- motivated behaviors (defensive treading) following AMPA receptor blockade. It is also important to understand the larger corticolimbic circuit in which NAc shell is embedded, and particularly to understand how corticolimbic top-down signals regulate generation of appetitive and defensive motivation by NAc. Aim 2 will identify which region of PFC is primarily responsible for modulation of subcortical unconditioned positive and negative motivation: medial OFC, infralimbic or prelimbic. Finally, it is important to understand how psychological context modulates NAc generation of fear and feeding by recruiting corticolimbic circuits. This phenomenon may be relevant to contextual influences on human pathological motivations, as well as to therapeutic interventions. Aim 3 will identify the particular PFC inputs to NAc that mediate environmental modulation of NAc-generation of motivation.

项目摘要 异常动机是各种人类精神障碍的重要特征。过度的食欲与药物成瘾和肥胖有关，有时会导致强迫性追求和过度消费药物或食物（1，2）。嵌入中质膜的电路中的伏隔核（NAC）在过度的激励动机中起着重要作用。 NAC的内侧外壳区域尤其与开胃动机行为的产生有关。除了在激励动机中扮演着众所周知的作用之外，中皮质胶系统还可以调解一些可怕的状态。该提案的重点是局部谷氨酸在鼻壳中的作用，在产生积极动机的行为中，例如强烈的喂养，以及谷氨酸破坏在NAC壳中产生负动机行为中的作用。中唇糖多巴胺（DA）系统与皮质脂蛋白比谷氨酸相互作用，以使食欲和恐惧的动机显着性（5）：AIM 1将确定D1或D2受体亚型是否对于在带动壳中产生任何一种积极动机的行为（饲料）是必不可少的AMPA受体阻滞后，动机行为（防御性踩踏）。也重要的是要了解NAC壳嵌入的较大的皮质脂质电路，尤其是要了解Corticolimbic上自上而下的信号如何调节NAC的起伏和防御动机的产生。 AIM 2将确定PFC的哪个区域主要负责调节皮质下无条件的积极和负动机：内侧OFC，Infralimbic或prelimbic。最后，重要的是要了解心理环境如何通过招募Corticolimbic电路来调节NAC的产生恐惧和喂养。这种现象可能与上下文对人类病理动机以及治疗性干预的影响有关。 AIM 3将确定NAC的特定PFC输入，以介导NAC生成动机的环境调节。