Effects of Systemic Administration of Oxytocin on Contextual Fear Extinction in a Rat Model of Post-Traumatic Stress Disorder
Effects of Systemic Administration of Oxytocin on Contextual Fear Extinction in a Rat Model of Post-Traumatic Stress Disorder
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发表时间：
2013
影响因子：
1.7
通讯作者：
Sharaf Eskandarian;Abbas Ali Vafaei;G. Vaezi;F. Taherian;Adel Kashefi;A. Rashidy-Pour
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作者：
Sharaf Eskandarian;Abbas Ali Vafaei;G. Vaezi;F. Taherian;Adel Kashefi;A. Rashidy-Pour
创伤后应激障碍（PTSD）的标志性症状之一是创伤记忆的消退受损。单次长时间应激（single extended stress，SPS）大鼠表现出恐惧消退障碍，因此被认为是PTSD的动物模型。催产素（OXT）最近被认为是治疗PTSD的潜在药物。在这项研究中，使用SPS大鼠，我们研究了多个系统的OXT管理上下文恐惧消退的影响。方法采用束缚2 h、强迫游泳20 min和乙醚麻醉3个阶段进行SPS，然后将其置于笼中静置7 d。在SPS组中，SPS治疗后7天，进行情境恐惧条件反射（第0天），然后在恐惧条件反射后连续4天进行消退训练。在假手术组中，除了不进行SPS处理之外，程序相似。结果在消退试验（10 min）中，记录了大鼠的冻结行为。每次消退试验后立即给予（I.P）OXT（1、10、100和1000µg/kg）。与假手术组相比，SPS组大鼠表现出明显的背景恐惧消退障碍。在恐惧条件化训练后24 h，SPS大鼠和Sham大鼠的冻结水平无显著差异，但在第二次消退训练后，SPS大鼠的冻结水平显著高于Sham大鼠。与假生理盐水处理的动物相比，全身OXT延迟假手术大鼠的恐惧消退。OXT对SPS大鼠无明显影响。讨论这些研究结果表明，增加OXT传输过程中的恐惧记忆再激活延迟恐惧消退，因此，OXT治疗PTSD的建议应谨慎考虑。
Introduction One of the hallmark symptoms of posttraumatic stress disorder (PTSD) is the impaired extinction of traumatic memory. Single prolonged stress (SPS) has been suggested as an animal model of PTSD, since SPS rats exhibited the impaired fear extinction. Oxytocin (OXT) has been recently suggested as a potential pharmacotherapy for treatment of PTSD. In this study, using SPS rats we investigated the effects of multiple systemic administration of OXT on contextual fear extinction. Methods SPS was conducted in three stages: restraint for 2 h, forced swim for 20 min, and diethyl ether anesthesia, and then left undisturbed in their home cage for 7 days. In the SPS group, 7 days after SPS treatment, contextual fear conditioning was performed (on day 0), and then extinction training was performed on each of four consecutive days following fear conditioning. In the sham group, the procedures were similar except that SPS treatment was not performed. Results During extinction trial (10 min) freezing behavior was recorded. OXT (1, 10, 100 and 1000µg/kg) was administrated (I.P) immediately after each extinction trial. SPS rats exhibited significant impairment of contextual fear extinction as compared with sham rats. While there was no significant difference in the freezing levels between SPS and Sham rats 24 h after the fear conditioning, the freezing levels in SPS rats were significantly higher than those in sham rats after the second extinction training. Systemic OXT delayed fear extinction in sham rats as compared with sham-saline treated animals. No effect of OXT was found in SPS rats. Discussion These findings indicate that increasing OXT transmission during fear memory reactivation delays fear extinction, and thus, the recommendation of OXT for PTSD treatment should be considered with caution.