The modulatory role of the lateral septum on neuroendocrine and behavioral stress responses.
The modulatory role of the lateral septum on neuroendocrine and behavioral stress responses.
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DOI：
10.1038/npp.2010.213
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发表时间：
2011-03
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--
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外侧隔（LS）已被证明在情绪过程和应激反应中起关键作用。然而，LS对应力调制的确切作用尚不清楚，因为先前的损伤研究大多使用电解损伤，从而破坏整个间隔区域，包括内侧组件和/或通道纤维。因此，本研究的目的是，研究选择性兴奋毒性消融LS对大鼠神经内分泌和行为应激反应的影响。双侧鹅膏蕈氨酸病变的LS增加下丘脑-垂体-肾上腺皮质（HPA）轴的反应，强迫游泳应激增强血浆促肾上腺皮质激素和皮质酮的反应和更高的应激诱导的c-Fos样免疫反应在下丘脑室旁核。此外，LS损伤的动物表现出更被动的应对方式，在强迫游泳试验中增加漂浮和减少挣扎/游泳行为与假损伤的控制。有趣的是，隔内皮质类固醇受体阻滞剂调制的行为应激应对，但未能改变HPA轴的应激反应。进一步的实验旨在阐明潜在的神经化学机制显示，隔内给药的选择性5-HT 1A受体拮抗剂WAY-100635增加和延长应激诱导的ACTH和皮质酮水平模仿病变的影响，而激动剂8-OH-DPAT抑制HPA轴的活动，促进LS的抑制作用。此外，8-OH-DPAT注射的动物表现出增加的主动和减少的被动应对策略，在强迫游泳，表明抗抑郁疗效。两者合计，我们的数据表明，LS促进积极的压力应对行为，并参与HPA抑制机制，至少部分介导的间隔5-HT 1A受体，不涉及糖皮质激素介导的反馈机制。
The lateral septum (LS) has been shown to have a key role in emotional processes and stress responses. However, the exact role of the LS on stress modulation is not clear, as previous lesion studies mostly used electrolytic lesions, thereby destroying the whole septal area, including medial components and/or fibers of passage. The aim of the present study was therefore, to investigate the effects of selective excitotoxic ablation of the LS on neuroendocrine and behavioral stress responses in rats. Bilateral ibotenic acid lesions of the LS increased hypothalamo–pituitary–adrenocortical (HPA) axis responses to forced swim stress indicated by enhanced plasma ACTH and corticosterone responses and higher stress-induced c-Fos-like immunoreactivity in the paraventricular hypothalamic nucleus. Moreover, LS-lesioned animals showed a more passive coping style in the forced swim test indicated by increased floating and reduced struggling/swimming behavior compared with sham-lesioned controls. Interestingly, intraseptal corticosteroid receptor blockade modulated behavioral stress coping but failed to change HPA axis stress responses. Further experiments aimed at elucidating underlying neurochemical mechanisms revealed that intraseptal administration of the selective 5-HT1A receptor antagonist WAY-100635 increased and prolonged stress-induced ACTH and corticosterone levels mimicking lesion effects, while the agonist 8-OH-DPAT suppressed HPA axis activity facilitating the inhibitory role of the LS. In addition, 8-OH-DPAT-injected animals showed increased active and decreased passive coping strategies during forced swimming suggesting antidepressant efficacy. Taken together, our data suggest that the LS promotes active stress coping behavior and is involved in a HPA-inhibitory mechanism that is at least in part mediated by septal 5-HT1A receptors and does not involve a glucocorticoid mediated feedback mechanism.
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