Joca Sâmia Regiane L, Padovan Cláudia Maria, Guimarães Francisco Silveira
Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
Braz J Psychiatry. 2003 Dec;25 Suppl 2:46-51. doi: 10.1590/s1516-44462003000600011. Epub 2004 Feb 16.
Stress exposure is an important factor in the development of depressive disorders. Although the mechanisms of this relationship are largely unknown, several pieces of evidence point to an involvement of the hippocampal formation: 1. stressful stimuli cause remodeling of hipocampal pyramidal cells and inhibit neurogenesis in the dentate gyrus. Antidepressive drugs attenuate these effects, probably by increasing the expression of neurotrophic factors; 2. facilitation of serotonergic neurotransmission in the hippocampus attenuates behavioral consequences of stress and produce antidepressive-like effects in several animal models; 3. antagonism of glutamate, the main excitatory neurotransmitter of the hippocampus, also induce antidepressive-like effects; 4. increased hippocampal activity has been described in genetically selected rats that are more sensitive to depression models. Similar result was found in depressive patients that fail to respond to antidepressant drugs; 5. together with the amygdala, the hippocampus plays a key role on consolidation and evocation of aversive memories. The challenge for the future will be to integrate the results from these different fields (clinical, electrophysiological, pharmacological and molecular) in an unifying theory about the role of the hippocampus on mood regulation, depressive disorder and antidepressant effects.
应激暴露是抑郁症发生发展的一个重要因素。尽管这种关系的机制在很大程度上尚不清楚，但有几条证据表明海马结构参与其中：1. 应激刺激会导致海马锥体细胞重塑，并抑制齿状回中的神经发生。抗抑郁药物可能通过增加神经营养因子的表达来减弱这些作用；2. 促进海马中的5-羟色胺能神经传递可减轻应激的行为后果，并在几种动物模型中产生类似抗抑郁的作用；3. 拮抗海马的主要兴奋性神经递质谷氨酸也可诱导类似抗抑郁的作用；4. 在对抑郁模型更敏感的基因选择大鼠中，已观察到海马活动增加。在对抗抑郁药物无反应的抑郁症患者中也发现了类似结果；5. 海马与杏仁核一起，在厌恶记忆的巩固和唤起中起关键作用。未来的挑战将是把这些不同领域（临床、电生理、药理和分子）的结果整合到一个关于海马在情绪调节、抑郁症和抗抑郁作用中作用的统一理论中。
