Role of Endocannabinoid System in Depressive Behavior

 描述(申请人提供)：与压力和抑郁相关的行为造成巨大的社会和经济代价，是全球自杀的主要原因。目前可用的治疗抑郁症的药物疗法是适度有效的，这强调了我们需要进一步了解抑郁症的神经生物学，并开发有效的药物疗法。抑郁症是一种复杂的、多因素的特征，有遗传和环境因素。有趣的是，抑郁症在女性中的患病率比男性更高。然而，这种性二型性的生物学基础尚不清楚。最近的研究表明，内源性大麻素(ECB)系统在调节情绪和情绪行为方面具有潜在的作用。然而，欧洲央行系统在抑郁行为中的作用尚不清楚。在这项研究中，我们将确定在使用应激(Wistar大鼠)和遗传(Wistar京都大鼠)模型以及重度抑郁症患者的死后脑中，与抑郁行为相关的ECB系统组件是否存在性别差异。我们将进一步评估针对欧洲央行系统的药物是否在啮齿动物模型中发挥抗抑郁药样作用。建议的研究将为欧洲中央银行系统在抑郁症神经生物学中的作用提供新的见解/S，可能有助于开发有效和个性化的药物治疗。

 DESCRIPTION (provided by applicant): Stress and depression related behaviors incur enormous social and economic costs, and are major leading causes of suicide worldwide. Currently available pharmacotherapies for depression are moderately effective, and that emphasizes the need to further our understanding of the neurobiology of depression and to develop effective pharmacotherapy. Depressive disorder is a complex and multifactorial trait with genetic and environmental contributing factors. Intriguingly, prevalence of depression is greater in women than men. However, the biological basis for this sexual dimorphism is not clearly understood. Recent studies have suggested a potential role for the endocannabinoid (eCB) system in mediating mood and emotional behaviors. However, the role of eCB system in depressive behavior is yet to be clearly understood. In this study, we will determine if there are any gender- specific differences in the components of eCB system associated with depressive behavior using stress (Wistar rat), and genetic (Wistar Kyoto rat) models and in postmortem brains of patients with major depression. We will further evaluate if drugs targeted to eCB system exert antidepressant-like effects in rodent models. The proposed studies would provide new insight/s into the role of eCB system in neurobiology of depression that might assist in the development of effective and personalized pharmacotherapy.