Dopamine terminal regions interact as a function of motivation and reinforcement

描述（由申请人提供）：大量证据表明，在自然（例如食物）和人工（例如药物）强化的神经生物学中，以及与目标寻求相关的动机状态中，存在中旋转边缘多巴胺（DA）系统，特别是内侧前额叶皮层（mPFC）和丘脑核（NAcc）。然而，关于这两个大脑区域如何作为动机状态或动机强度的变化的函数相互作用，或者这种相互作用如何修改目标导向行为的输出，相对来说很少。因此，目前的建议是为了更好地了解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，建立与c-Fos（神经元激活的蛋白质标记物）通过采用在体内微透析获得的初步数据，以进一步了解mPFC和NAcc之间的相互作用作为操纵的动机状态和神经元数量的函数。其次，评估mPFC和NAcc的化学抑制和激发的影响，因为它与动机的多个行为指数有关（即响应食物强化的递进比率;操作跑道中的条件接近行为）。第三，评估D1/D2拮抗作用在mPFC和NAcc中对相同行为测定中性能的影响。了解mPFC和NAcc之间的功能关系，因为它涉及到动机，将提供有关神经系统用于组织行为的过程的关键证据。对人类和动物的大量研究表明，这项研究中所研究的大脑区域是成瘾以及其他具有动机成分的行为障碍的关键介质。因此，完全了解这些大脑区域的功能是必要的，以充分解决一些重要的公共卫生问题。

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.