Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, USA.
J Psychopharmacol. 2013 Dec;27(12):1090-106. doi: 10.1177/0269881113490328. Epub 2013 May 23.
Over 20 years ago, Deakin and Graeff hypothesized about the role of different serotonergic pathways in controlling the behavioral and physiologic responses to aversive stimuli, and how compromise of these pathways could lead to specific symptoms of anxiety and affective disorders. A growing body of evidence suggests these serotonergic pathways arise from topographically organized subpopulations of serotonergic neurons located in the dorsal and median raphe nuclei. We argue that serotonergic neurons in the dorsal/caudal parts of the dorsal raphe nucleus project to forebrain limbic regions involved in stress/conflict anxiety-related processes, which may be relevant for anxiety and affective disorders. Serotonergic neurons in the "lateral wings" of the dorsal raphe nucleus provide inhibitory control over structures controlling fight-or-flight responses. Dysfunction of this pathway could be relevant for panic disorder. Finally, serotonergic neurons in the median raphe nucleus, and the developmentally and functionally-related interfascicular part of the dorsal raphe nucleus, give rise to forebrain limbic projections that are involved in tolerance and coping with aversive stimuli, which could be important for affective disorders like depression. Elucidating the mechanisms through which stress activates these topographically and functionally distinct serotonergic pathways, and how dysfunction of these pathways leads to symptoms of neuropsychiatric disorders, may lead to the development of novel approaches to both the prevention and treatment of anxiety and affective disorders.
20 多年前，迪肯和格雷夫假设了不同的 5-羟色胺能途径在控制对厌恶刺激的行为和生理反应中的作用，以及这些途径的损伤如何导致焦虑和情感障碍的特定症状。越来越多的证据表明，这些 5-羟色胺能途径源于位于中缝背核和中缝核的 5-羟色胺能神经元的拓扑组织亚群。我们认为，中缝背核背/尾部分的 5-羟色胺能神经元投射到参与应激/冲突相关焦虑过程的前脑边缘区域，这可能与焦虑和情感障碍有关。中缝背核“侧翼”的 5-羟色胺能神经元对控制战斗或逃跑反应的结构提供抑制性控制。该途径的功能障碍可能与惊恐障碍有关。最后，中缝核和中缝背核的发育和功能相关的连合间部分的 5-羟色胺能神经元，在前脑边缘投射中产生作用，参与对厌恶刺激的耐受和应对，这可能对抑郁症等情感障碍很重要。阐明应激通过这些拓扑和功能上不同的 5-羟色胺能途径激活的机制，以及这些途径的功能障碍如何导致神经精神障碍的症状，可能会为焦虑和情感障碍的预防和治疗带来新的方法。
