Department of Psychology and the Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar Ilan University, Ramat Gan 5290002, Israel.
The Mina and Everard Goodman Faculty of Life Sciences and the Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar Ilan University, Ramat Gan 5290002, Israel.
Int J Mol Sci. 2021 Feb 13;22(4):1867. doi: 10.3390/ijms22041867.
Depression, the most prevalent psychiatric disorder in the Western world, is characterized by increased negative affect (i.e., depressed mood, cost value increase) and reduced positive affect (i.e., anhedonia, reward value decrease), fatigue, loss of appetite, and reduced psychomotor activity except for cases of agitative depression. Some forms, such as post-partum depression, have a high risk for suicidal attempts. Recent studies in humans and in animal models relate major depression occurrence and reoccurrence to alterations in dopaminergic activity, in addition to other neurotransmitter systems. Imaging studies detected decreased activity in the brain reward circuits in major depression. Therefore, the location of dopamine receptors in these circuits is relevant for understanding major depression. Interestingly, in cortico-striatal-dopaminergic pathways within the reward and cost circuits, the expression of dopamine and its contribution to reward are modulated by endocannabinoid receptors. These receptors are enriched in the striosomal compartment of striatum that selectively projects to dopaminergic neurons of substantia nigra compacta and is vulnerable to stress. This review aims to show the crosstalk between endocannabinoid and dopamine receptors and their vulnerability to stress in the reward circuits, especially in corticostriatal regions. The implications for novel treatments of major depression are discussed.
抑郁症是西方世界最常见的精神障碍,其特征是负性情绪增加(即抑郁心境、成本价值增加)和正性情绪减少(即快感缺失、奖赏价值降低)、疲劳、食欲减退和精神运动活动减少,但激越性抑郁症除外。一些形式,如产后抑郁症,自杀企图的风险很高。最近在人类和动物模型中的研究表明,除了其他神经递质系统外,主要抑郁症的发生和复发与多巴胺能活动的改变有关。影像学研究发现,在主要抑郁症的大脑奖励回路中,活动减少。因此,多巴胺受体在这些回路中的位置对于理解主要抑郁症是相关的。有趣的是,在奖励和成本回路中的皮质纹状体多巴胺能通路中,多巴胺的表达及其对奖励的贡献受到内源性大麻素受体的调节。这些受体在纹状体的纹状体区富集,选择性投射到黑质致密部的多巴胺能神经元,容易受到压力的影响。本综述旨在展示内源性大麻素和多巴胺受体之间的串扰及其在奖励回路中的易感性,特别是在皮质纹状体区域。讨论了对主要抑郁症的新型治疗方法的影响。