Kincheski Grasielle C, Carobrez Antonio P
Departamento de Farmacologia, CCB, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
Behav Brain Res. 2010 Jan 5;206(1):120-6. doi: 10.1016/j.bbr.2009.09.001. Epub 2009 Sep 6.
Elevated plus-maze (EPM) experienced rats show reduced open arms exploration in a subsequent EPM exposure, expressing the increased open arms avoidance which is characteristic of anxiety/fear-like behavior. The midbrain dorsal periaqueductal gray (dPAG) is an important integrative area of the neuroaxis able to control the motivational states of an animal. It has been shown that dPAG participates in the mediation of anxiety/fear-like behavior elicited in the EPM. The present study was outlined to evaluate the dPAG-NMDA-receptor contribution to the increased open arms avoidance found in EPM experienced rats. In addition, a possible mnemonic effect, due to the dPAG-NMDA-receptor blockade, was tested in the step-down inhibitory avoidance task (SD). Male Wistar rats received dPAG infusion of NMDA antagonists (AP5 or ifenprodil) before being submitted to the EPM test and retest sessions, or the SD training and test sessions. Both NMDA-receptor antagonists infused in the dPAG, reduced the fear-like behavior exhibited in the EPM by increasing the open arms exploration in both naïve and EPM experienced rats. In addition, the dPAG-NMDA-receptor blockade also reduced the latency to SD during the retrieval without interfering with the acquisition or the consolidation of the inhibitory avoidance. These results suggest that the NMDA-receptor dPAG activation could underlie the defensive response evoked in the EPM test and retest and also the retrieval of aversive memories involved in the SD. The results support the notion that the dPAG is a key structure in the modulation of the best behavioral strategy to cope with aversive contexts.
在高架十字迷宫（EPM）中经历过的大鼠，在后续再次暴露于EPM时，其在开放臂的探索减少，表现出开放臂回避增加，这是焦虑/恐惧样行为的特征。中脑导水管周围灰质背侧（dPAG）是神经轴的一个重要整合区域，能够控制动物的动机状态。已经表明，dPAG参与介导EPM中引发的焦虑/恐惧样行为。本研究旨在评估dPAG-NMDA受体对EPM经历大鼠中观察到的开放臂回避增加的作用。此外，在阶梯式抑制回避任务（SD）中测试了由于dPAG-NMDA受体阻断可能产生的记忆效应。雄性Wistar大鼠在接受EPM测试和重新测试，或SD训练和测试之前，接受dPAG内注射NMDA拮抗剂（AP5或ifenprodil）。注射到dPAG中的两种NMDA受体拮抗剂，均通过增加未经历过EPM的大鼠和经历过EPM的大鼠在开放臂的探索，从而减少了EPM中表现出的恐惧样行为。此外，dPAG-NMDA受体阻断在记忆提取期间也减少了进入SD的潜伏期，而不干扰抑制回避的获得或巩固。这些结果表明，NMDA受体dPAG激活可能是EPM测试和重新测试中诱发的防御反应以及SD中涉及的厌恶记忆提取的基础。这些结果支持了dPAG是调节应对厌恶情境的最佳行为策略的关键结构这一观点。
