Laboratório de Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Neuroscience. 2012 Sep 6;219:72-81. doi: 10.1016/j.neuroscience.2012.06.005. Epub 2012 Jun 12.
It is well known that excitatory amino acids induce unconditioned fear responses when locally injected into the dorsal periaqueductal gray matter (dPAG). However, there are only few studies about the involvement of excitatory amino acids mediation in dPAG in the expression of conditioned fear. The present series of experiments evaluates the participation of AMPA/Kainate and NMDA glutamatergic receptors of dPAG in the expression of conditioned fear, assessed by the fear-potentiated startle (FPS) and conditioned freezing responses. Wistar rats were subjected to fear conditioning to light. Twenty-four hours later, they received intra-dPAG injections of kainic acid or NMDA (AMPA/Kainate and NMDA agonists) and 1,2,3,4-Tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium salt hydrate (NBQX) or D(-)-2-Amino-7-phosphonoheptanoic acid (AP7) (AMPA/Kainate and NMDA antagonists) and were submitted to the FPS test. Conditioned freezing response was simultaneously measured. Effects of drug treatment on motor activity were evaluated in the open-field test. Intra-dPAG injections of glutamatergic agonists enhanced conditioned freezing and promoted pro-aversive effects in the FPS. Lower doses of the agonists had no effect or enhanced FPS whereas higher doses disrupted FPS, indicating a non-monotonic relationship between fear and FPS. The antagonist NBQX had no significant effects while AP7 decreased conditioned freezing but did not affect FPS. Both antagonists reduced the effects of the agonists. The obtained results cannot be attributed to motor deficits. The results suggest an important role of the AMPA/Kainate and NMDA mechanisms of the dPAG in the expression of conditioned freezing and FPS.
众所周知，当兴奋性氨基酸局部注射到背侧穹窿周灰质（dPAG）时，会引起无条件恐惧反应。然而，关于 dPAG 中兴奋性氨基酸介导在条件性恐惧表达中的作用的研究很少。本系列实验评估了 dPAG 中 AMPA/Kainate 和 NMDA 谷氨酸能受体在条件性恐惧表达中的参与，通过恐惧增强的惊跳（FPS）和条件性冻结反应来评估。Wistar 大鼠接受光条件恐惧训练。24 小时后，它们接受了 dPAG 内注射海人酸或 NMDA（AMPA/Kainate 和 NMDA 激动剂）和 1,2,3,4-四氢-6-硝基-2,3-二氧代-苯并[f]喹喔啉-7-磺酰胺二钠盐水合物（NBQX）或 D(-)-2-氨基-7-磷基庚酸（AP7）（AMPA/Kainate 和 NMDA 拮抗剂），并进行了 FPS 测试。同时测量了条件性冻结反应。在旷场测试中评估了药物治疗对运动活动的影响。dPAG 内注射谷氨酸能激动剂增强了条件性冻结，并在 FPS 中促进了厌恶效应。较低剂量的激动剂没有作用或增强了 FPS，而较高剂量的激动剂破坏了 FPS，表明恐惧和 FPS 之间存在非单调关系。拮抗剂 NBQX 没有显著影响，而 AP7 降低了条件性冻结，但不影响 FPS。两种拮抗剂都降低了激动剂的作用。所得结果不能归因于运动缺陷。结果表明，dPAG 中的 AMPA/Kainate 和 NMDA 机制在条件性冻结和 FPS 的表达中起着重要作用。
