Effects of systemic glutamatergic manipulations on conditioned eyeblink responses and hyperarousal in a rabbit model of post-traumatic stress disorder.
Effects of systemic glutamatergic manipulations on conditioned eyeblink responses and hyperarousal in a rabbit model of post-traumatic stress disorder.
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DOI：
10.1097/fbp.0000000000000333
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发表时间：
2017-10
影响因子：
1.6
通讯作者：
Schreurs BG
中科院分区：
文献类型：
--
作者：
Burhans LB;Smith-Bell CA;Schreurs BG
谷氨酸能功能障碍与许多神经精神疾病有关，包括创伤后应激障碍（PTSD）。谷氨酸拮抗剂在治疗PTSD症状方面显示出一定的效用，而谷氨酸激动剂可能促进认知行为疗法的效果。我们基于兔子眨眼反应的条件反射建立了一个PTSD动物模型，该模型涉及两个关键特征：对与厌恶事件相关线索的条件反应（CRs）以及一种被称为条件特异性反射改变（CRM）的条件性过度警觉形式。减少CRs和CRM的最佳治疗方法是非配对消退。本研究的目的是检验使用N - 甲基 - D - 天冬氨酸（NMDA）谷氨酸受体拮抗剂氯胺酮治疗是否可以减少CRs和CRM，以及NMDA激动剂D - 环丝氨酸与非配对消退治疗相结合是否可以增强两者的消退。给予单剂量的亚麻醉剂量氯胺酮对CRs或CRM没有显著的即时或延迟效应。将D - 环丝氨酸与单日非配对消退相结合在短期内促进了CRs的消退，但对CRM没有影响。这些结果提醒我们，治疗可能改善PTSD症状的一个方面，而对其他症状没有显著影响，这强调了对PTSD采用多种治疗方法以及建立涉及多种症状的动物模型的重要性。
Glutamatergic dysfunction is implicated in many neuropsychiatric conditions including post-traumatic stress disorder (PTSD). Glutamate antagonists have shown some utility in treating PTSD symptoms while glutamate agonists may facilitate cognitive behavioral therapy outcomes. We have developed an animal model of PTSD, based on conditioning of the rabbit's eyeblink response, that addresses two key features: conditioned responses (CRs) to cues associated with an aversive event and a form of conditioned hyperarousal referred to as conditioning-specific reflex modification (CRM). The optimal treatment to reduce both CRs and CRM is unpaired extinction. The goals of the study were to examine whether treatment with the NMDA glutamate receptor antagonist ketamine could reduce CRs and CRM, and if the NMDA agonist d-cycloserine combined with unpaired extinction treatment could enhance extinction of both. Administration of a single-dose of subanesthetic ketamine had no significant immediate or delayed effect on CRs or CRM. Combining d-cycloserine with a single day of unpaired extinction facilitated extinction of CRs short-term while having no impact on CRM. These results caution that treatments may improve one aspect PTSD-symptomology while having no significant effects on other symptoms, stressing the importance of a multiple-treatment approach to PTSD and animal models that address multiple symptoms.