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在大鼠高架十字迷宫实验中揭示了腹侧和背侧海马体不同的AP5抗焦虑作用。

Distinct ventral and dorsal hippocampus AP5 anxiolytic effects revealed in the elevated plus-maze task in rats.

作者信息

Nascimento Häckl Luciane Pereira, Carobrez Antônio Pádua

机构信息

Departamento de Farmacologia, CCB, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.

出版信息

Neurobiol Learn Mem. 2007 Sep;88(2):177-85. doi: 10.1016/j.nlm.2007.04.007. Epub 2007 May 30.

Abstract

The hippocampal formation (HPC) mediates processes associated with learning, memory, anxiety and fear. The glutamate N-methyl-d-aspartate (NMDA)-receptor subtype is involved in many HPC functional processes related to learning and memory. Although not tested for the HPC, NMDA-receptor antagonists reduced fear and anxiety related responses when applied to other brain regions mediating defensive behaviour. Consequently, this study evaluated the effects of ventral or dorsal HPC application of the NMDA-receptor antagonist, AP5, in rats submitted to the Trial 1/Trial 2 elevated plus-maze (EPM) task. Ventral, but not dorsal, infusions of AP5 (6 and 24 nmol) before EPM Trial 1 increased open arms exploration and reduced risk assessment behavior, suggesting an anxiolytic-like effect. Furthermore, no interference in the avoidance responses was detected during EPM Trial 2 after AP5 infusion into the ventral or dorsal HPC before Trial 1, post-trial 1, or before Trial 2. These data support the notion of differential involvement of ventral HPC, but not dorsal, in mechanisms associated with anxiety and suggest the participation of the glutamatergic transmission, through NMDA receptor, into the ventral HPC in the mediation of defensive behavior.

摘要

海马结构(HPC)介导与学习、记忆、焦虑和恐惧相关的过程。谷氨酸N-甲基-D-天冬氨酸(NMDA)受体亚型参与许多与学习和记忆相关的HPC功能过程。尽管尚未对HPC进行测试,但当将NMDA受体拮抗剂应用于介导防御行为的其他脑区时,其可减少与恐惧和焦虑相关的反应。因此,本研究评估了在接受试验1/试验2高架十字迷宫(EPM)任务的大鼠中,向腹侧或背侧HPC应用NMDA受体拮抗剂AP5的效果。在EPM试验1之前,向腹侧而非背侧注入AP5(6和24 nmol)可增加开放臂探索并减少风险评估行为,提示有类似抗焦虑的作用。此外,在试验1之前、试验1后或试验2之前向腹侧或背侧HPC注入AP5后,在EPM试验2期间未检测到对回避反应的干扰。这些数据支持腹侧HPC而非背侧HPC在与焦虑相关机制中存在不同参与度的观点,并表明通过NMDA受体的谷氨酸能传递参与腹侧HPC介导的防御行为。

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