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背侧和腹侧海马体中的NMDA-NO信号通路可随时间调节对强迫游泳应激的行为反应。

NMDA-NO signaling in the dorsal and ventral hippocampus time-dependently modulates the behavioral responses to forced swimming stress.

作者信息

Diniz Cassiano R A F, Casarotto Plínio C, Joca Sâmia R L

机构信息

School of Medicine, Campus USP, Ribeirão Preto, SP 14049-900, Brazil.

School of Medicine, Campus USP, Ribeirão Preto, SP 14049-900, Brazil; Neuroscience Center, University of Helsinki, Finland.

出版信息

Behav Brain Res. 2016 Jul 1;307:126-36. doi: 10.1016/j.bbr.2016.03.037. Epub 2016 Mar 22.

DOI:10.1016/j.bbr.2016.03.037
PMID:27016428
Abstract

Hodological and genetic differences between dorsal (DH) and ventral (VH) hippocampus may convey distinct behavioral roles. DH is responsible for mediating cognitive process, such as learning and memory, while VH modulates neuroendocrine and emotional-motivational responses to stress. Manipulating glutamatergic NMDA receptors and nitric oxide (NO) systems of the hippocampus induces important changes in behavioral responses to stress. Nevertheless, there is no study concerning functional differences between DH and VH in the modulation of behavioral responses induced by stress models predictive of antidepressant effects. Thus, this study showed that reversible blockade of the DH or VH of animals submitted to the forced swimming test (FST), by using cobalt chloride (calcium-dependent synaptic neurotransmission blocker), was not able to change immobility time. Afterwards, the NMDA-NO system was evaluated in the FST by means of intra-DH or intra-VH administration of NMDA receptor antagonist (AP7), NOS1 and sGC inhibitors (N-PLA and ODQ, respectively). Bilateral intra-DH injections after pretest or before test were able to induce antidepressant-like effects in the FST. On the other hand, bilateral VH administration of AP-7, N-PLA and ODQ induced antidepressant-like effects only when injected before the test. Administration of NO scavenger (C-PTIO) intra-DH, after pretest and before test, or intra-VH before test induced similar results. Increased NOS1 levels was associated to stress exposure in the DH. These results suggest that the glutamatergic-NO system of the DH and VH are both able to modulate behavioral responses in the FST, albeit with differential participation along time after stress exposure.

摘要

背侧海马体(DH)和腹侧海马体(VH)之间的神经通路及基因差异可能具有不同的行为学作用。DH负责介导认知过程,如学习和记忆,而VH则调节对压力的神经内分泌和情绪 - 动机反应。操纵海马体的谷氨酸能NMDA受体和一氧化氮(NO)系统会引起对应激行为反应的重要变化。然而,尚无关于在预测抗抑郁作用的应激模型所诱导的行为反应调节中,DH和VH功能差异的研究。因此,本研究表明,通过使用氯化钴(钙依赖性突触神经传递阻滞剂)对接受强迫游泳试验(FST)的动物的DH或VH进行可逆性阻断,未能改变不动时间。之后,在FST中通过向DH或VH内注射NMDA受体拮抗剂(AP7)、NOS1和sGC抑制剂(分别为N - PLA和ODQ)来评估NMDA - NO系统。在预试验后或试验前进行双侧DH内注射能够在FST中诱导出抗抑郁样效应。另一方面,仅在试验前注射时,向VH双侧注射AP - 7、N - PLA和ODQ才会诱导出抗抑郁样效应。在预试验后和试验前向DH内注射NO清除剂(C - PTIO),或在试验前向VH内注射,会产生类似结果。DH中NOS1水平升高与应激暴露有关。这些结果表明,DH和VH的谷氨酸能 - NO系统均能够调节FST中的行为反应,尽管在应激暴露后的不同时间参与程度有所不同。

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