Development of rat models of the effort-related symptoms of depression

描述（申请人提供）：临床心理学家和精神病学家已经开始强调与努力相关的症状的重要性，如无活力，冷漠和疲劳，在重度抑郁症中。然而，尽管目前有大量的测试可用于在动物模型中评估抗抑郁药物，但没有一个广泛使用的任务是专门针对动物中与努力相关的功能。在过去的几年里，我们的实验室已经开发出动物行为模型，用于评估各种神经递质，如多巴胺（DA）和腺苷，在努力和努力相关的选择行为中的作用。相当多的证据表明，这些动物基础研究对于理解人类与努力相关的功能障碍具有潜在的相关性。然而，确定这些程序是否可以导致抑郁症与努力相关症状的新模型的开发至关重要。由于这些原因，建议调查的目标是研究与抑郁症有关的几种条件的能力 来诱导大鼠的努力相关功能障碍。一组研究将评估低剂量的单胺消耗剂利血平对涉及努力和努力相关选择行为的任务的影响。其他实验将研究的行为特征， 两种抑郁症的遗传模型（先天无助大鼠;弗林德斯敏感线大鼠）。最后一组研究将使用努力相关功能的行为模型，评估一种新的抑郁症治疗策略（腺苷A2 A拮抗剂）和两种众所周知的药物（安非他酮和氟西汀）的效果。拟议的实验旨在测试使用这些程序作为抑郁症和其他疾病的努力相关症状的潜在模型的可行性。

DESCRIPTION (provided by applicant): Clinical psychologists and psychiatrists have come to emphasize the importance of effort-related symptoms, such as anergia, apathy, and fatigue, in major depression. Nevertheless, despite the large number of tests that are currently available for the assessment of antidepressant drugs in animal models, none of the widely used tasks is specifically focused upon effort-related functions in animals. Over the last few years, our laboratory has developed behavioral models in animals that are useful for assessing the role of various neurotransmitters, such as dopamine (DA) and adenosine, in the exertion of effort and effort-related choice behavior. Considerable evidence indicates that these basic studies in animals are potentially relevant for understanding effort-related dysfunction in humans. However, it is critical to determine if these procedures can lead to the development of novel models of the effort- related symptoms of depression. For these reasons, the goal of the proposed investigation is to study the ability of several conditions that are related to depression to induce effort-related dysfunctions in rats. One group of studies will assess the effects of low doses of the monoamine-depleting agent reserpine on tasks involving exertion of effort and effort-related choice behavior. Additional experiments will study the behavioral characteristics of two genetic models of depression (Congenitally Helpless Rats; Flinders Sensitive line rats). The final group of studies will assess the effects of a novel treatment strategy for depression (adenosine A2A antagonists) and two well known drugs (bupropion and fluoxetine), using behavioral models of effort-related function. The proposed experiments are designed to test the feasibility of using these procedures as potential models of the effort-related symptoms of depression and other disorders.