Effort-related Functions of Nucleus Accumbens Adenosine A2A Receptors

描述(由申请者提供)：在心理学和精神病学文献中，动机行为具有活力或激活性成分的概念是一个反复出现的主题。许多研究者强调，在寻求刺激的行为中，工作输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，根据对激励价值和响应成本的评估，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，如精神运动减慢和冷漠，在各种临床症状中。由于行为激活过程的科学重要性和临床相关性，研究其中涉及的大脑机制是至关重要的。大量证据表明，伏核中的多巴胺(DA)调节行为激活过程。伏隔核DA耗竭对觅食行为的影响在很大程度上取决于任务的工作要求，而伏隔核DA传递的干扰对努力相关的决策产生强大的影响。然而，应该认识到，伏隔核多巴胺只是调节动机的激活方面的大脑回路的一个组成部分。中脑边缘DA被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，在包括伏隔核在内的纹状体区域，DA和腺苷A2a受体之间存在功能上的相互作用。这种相互作用通常是在与帕金森症相关的动物模型的背景下进行研究的，但对伏隔核中腺苷A2a受体与努力相关的功能知之甚少。因此，拟议的实验将集中在伏隔核中腺苷A2a受体的努力相关功能。假设阻断伏核内的腺苷A2a受体将逆转DA拮抗和伏核DA耗竭的行为效应，局部刺激腺苷A2a受体将以类似于干扰DA传递的方式改变努力的施加和努力相关的决策。从心理健康的角度来看，研究腺苷A2a受体在努力相关过程中的作用是至关重要的，因为这样的研究可以提供关于动机的一个基本方面的信息，还因为它们可能导致开发出治疗与能量相关的疾病的新方法，例如抑郁症中精神运动减慢、麻木或冷漠。

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.