Effort-related Functions of Nucleus Accumbens Adenosine A2A Receptors

描述（由申请人提供）：动机行为具有能量或激活成分的概念是心理学和精神病学文献中反复出现的主题。许多研究者强调，刺激寻求行为中工作产出的活力或持久性是动机的一个基本方面。生物体不断地根据成本/收益分析做出与努力相关的决策，根据对动机价值和反应成本的评估将资源分配到目标导向的行为中。在临床文献中，精神病学家和心理学家已经开始强调能量相关功能障碍的重要性，例如精神迟钝和冷漠，在各种临床综合征中。由于行为激活过程的科学重要性和临床相关性，研究所涉及的大脑机制至关重要。大量的证据表明，中脑背外侧核的多巴胺（DA）调节行为激活过程。多巴胺耗竭对食物搜寻行为的影响在很大程度上取决于任务的工作要求，干扰多巴胺的传输对努力相关的决策产生了强大的影响。然而，应该认识到，多巴胺只是大脑回路中调节动机激活方面的一个组成部分。中脑边缘DA嵌入到涉及其他脑区和递质的更大的神经过程网络中。有证据表明，DA和腺苷A2 A受体在纹状体区域，包括延髓核之间存在功能性相互作用。这种相互作用通常是在与帕金森病相关的动物模型的背景下研究的，但对腺苷A2 A受体在丘脑核中的努力相关功能知之甚少。因此，拟议的实验将集中在腺苷A2 A受体的努力相关的功能在丘脑核。据推测，阻断腺苷A2 A受体在丘脑核将逆转DA拮抗和丘脑DA耗竭的行为效应，腺苷A2 A受体的局部刺激将改变努力和努力相关的决策的方式是类似的干扰DA传输的影响。从心理健康的角度来看，研究腺苷A2 A受体在与努力相关的过程中的作用至关重要，因为这些研究可以提供有关动机的基本方面的信息，也因为它们可能导致开发新的治疗方法用于能量相关疾病，如抑郁症，运动障碍或冷漠中的精神障碍。

DESCRIPTION (provided by applicant): The notion that motivated behaviors have an energetic or activational component is a recurring theme in the literatures of psychology and psychiatry. Many researchers have emphasized that the vigor or persistence of work output in stimulus-seeking behavior is a fundamental aspect of motivation. Organisms continually make effort-related decisions based upon cost/benefit analyses, allocating resources into goal- directed behaviors based upon assessments of motivational value and response costs. In the clinical literature, psychiatrists and psychologists have come to emphasize the importance of energy-related dysfunctions, such as psychomotor slowing and apathy, in various clinical syndromes. Because of the scientific importance and clinical relevance of behavioral activation processes, it is critical to investigate the brain mechanisms involved. Considerable evidence indicates that dopamine (DA) in nucleus accumbens regulates behavioral activation processes. The effects of accumbens DA depletions on food-seeking behavior depend greatly upon the work requirements of the task, and interference with accumbens DA transmission exerts a powerful influence over effort-related decision making. Nevertheless, it should be recognized that accumbens DA only functions as one component of the brain circuitry regulating activational aspects of motivation. Mesolimbic DA is embedded into a larger network of neural processes involving other brain areas and transmitters. Evidence indicates that there is a functional interaction between DA and adenosine A2A receptors in striatal areas, including the nucleus accumbens. This interaction typically is studied in the context of animal models related to parkinsonism, but less is known about the effort-related functions of adenosine A2A receptors in nucleus accumbens. Therefore, the proposed experiments will focus upon the effort-related functions of adenosine A2A receptors in the nucleus accumbens. It is hypothesized that blockade of adenosine A2A receptors in nucleus accumbens will reverse the behavioral effects of DA antagonism and accumbens DA depletion, and that local stimulation of adenosine A2A receptors will alter the exertion of effort and effort-related decision making in a manner that is similar to the effects of interference with DA transmission. From a mental health perspective, it is vital to study the role of adenosine A2A receptors in effort-related processes because such studies could provide information about a fundamental aspect of motivation, and also because they could lead to the development of novel treatments for energy-related disorders such as psychomotor slowing in depression, anergia or apathy.