Effects of ketamine, dexmedetomidine and propofol anesthesia on emotional memory consolidation in rats: Consequences for the development of post-traumatic stress disorder
Effects of ketamine, dexmedetomidine and propofol anesthesia on emotional memory consolidation in rats: Consequences for the development of post-traumatic stress disorder
复制标题
DOI：
10.1016/j.bbr.2017.04.048
复制
发表时间：
2017-06-30
影响因子：
2.7
通讯作者：
Campolongo, Patrizia
中科院分区：
文献类型：
--
作者：
Morena, Maria;Berardi, Andrea;Campolongo, Patrizia
重症监护病房（ICU）或急诊室的病人，暴露于创伤事件，是在创伤后应激障碍（PTSD）发展的风险增加。常用的镇静剂/麻醉剂可以干扰记忆形成的机制，加重或减弱创伤事件的记忆，并随后促进或降低PTSD发展的风险。在这里，我们评估了氯胺酮，右美托咪定和丙泊酚对恐惧记忆巩固以及随后与创伤应激暴露相关的认知和情绪改变的影响。在抑制性回避训练后，立即向大鼠腹膜内注射氯胺酮（100-125 mg/kg）、右美托咪啶（0.3-0.4 mg/kg）或其载体，并测试48 h记忆保持。此外，在大鼠PTSD模型中，在药物注射后两周评价氯胺酮（125 mg/kg）、右美托咪定（0.4 mg/kg）、丙泊酚（300 mg/kg）或其载体对长期记忆和社会互动的影响。氯胺酮麻醉增加了PTSD模型的记忆保留，而不改变创伤记忆强度。然而，氯胺酮引起了长期的社会行为减少。相反，右美托咪定显著损害记忆保持，而不影响PTSD模型中的长期认知或情感行为。我们以前已经证明，异丙酚麻醉增强48小时记忆保持。在此，我们发现丙泊酚在PTSD模型中诱导了持久的创伤记忆增强和焦虑作用。这些发现为临床研究提供了新的证据，表明在急诊和ICU中使用氯胺酮或丙泊酚麻醉可能更容易促进PTSD的发展，而右美托咪定可能具有预防作用。
Intensive Care Unit (ICU) or emergency care patients, exposed to traumatic events, are at increased risk for Post Traumatic Stress Disorder (PTSD) development. Commonly used sedative/anesthetic agents can interfere with the mechanisms of memory formation, exacerbating or attenuating the memory for the traumatic event, and subsequently promote or reduce the risk of PTSD development. Here, we evaluated the effects of ketamine, dexmedetomidine and propofol on fear memory consolidation and subsequent cognitive and emotional alterations related to traumatic stress exposure. Immediately following an inhibitory avoidance training, rats were intraperitoneally injected with ketamine (100-125 mg/kg), dexmedetomidine (0.3-0.4 mg/kg) or their vehicle and tested for 48 h memory retention. Furthermore, the effects of ketamine (125 mg/kg), dexmedetomidine (0.4 mg/kg), propofol (300 mg/kg) or their vehicle on long-term memory and social interaction were evaluated two weeks after drug injection in a rat PTSD model. Ketamine anesthesia increased memory retention without altering the traumatic memory strength in the PTSD model. However, ketamine induced a long-term reduction of social behavior. Conversely, dexmedetomidine markedly impaired memory retention, without affecting long-lasting cognitive or emotional behaviors in the PTSD model. We have previously shown that propofol anesthesia enhanced 48 h memory retention. Here, we found that propofol induced an enduring traumatic memory enhancement and anxiogenic effects in the PTSD model. These findings provide new evidence for clinical studies showing that the use of ketamine or propofol anesthesia in emergency care and ICU might be more likely to promote the development of PTSD, while dexmedetomidine might have prophylactic effects.