Trauma patients treated with ketamine during emergency care present aggravated early post- traumatic stress reaction which is highly predictive of post-traumatic stress disorder (PTSD) development and severity. The use of ketamine in the acute trauma phase may directly or indirectly interfere with neural processes of memory consolidation of the traumatic event, thus leading to the formation of maladaptive memories, a hallmark symptom of PTSD. We have recently shown that ketamine anesthesia, immediately after a traumatic event, enhances memory consolidation and leads to long-lasting alterations of social behavior in rats. Based on the evidence that ketamine induces a robust central and peripheral adrenergic/noradrenergic potentiation and that activation of this system is essential for the formation of memory for stressful events, we explored the possibility that the strong sympathomimetic action of ketamine might underlie its memory enhancing effects. We found that rats given immediate, but not delayed, post-training ketamine anesthesia (125 mg/kg) presented enhanced 48-h memory retention in an inhibitory avoidance task and that these effects were blocked by adrenal medullectomy, lesions of the locus coeruleus, systemic or intra-basolateral amygdala ß-adrenergic receptor antagonism. Thus, the memory enhancing effects of ketamine anesthesia are time-dependent and mediated by a combined peripheral-central sympathomimetic action. We elucidated a mechanism by which ketamine exacerbates acute post-traumatic reaction, possibly leading to development of PTSD symptomatology later in life. These findings will help guide for a better management of sedation/anesthesia in emergency care to promote the prophylaxis and reduce the risk of developing trauma-related disorders in trauma victims.

在紧急护理期间用氯胺酮治疗的创伤患者呈现加重的早期创伤后应激反应，这高度预测创伤后应激障碍 (PTSD) 的发展和严重程度。在急性创伤阶段使用氯胺酮可能直接或间接干扰创伤事件记忆巩固的神经过程，从而导致适应不良记忆的形成，这是 PTSD 的标志性症状。我们最近表明，氯胺酮麻醉在创伤性事件发生后立即增强记忆巩固并导致大鼠社会行为的长期改变。基于氯胺酮诱导强大的中枢和外周肾上腺素能/去甲肾上腺素能增强的证据，并且该系统的激活对于压力事件记忆的形成至关重要，我们探讨了氯胺酮强烈的拟交感神经作用可能是其记忆增强作用的基础。我们发现，大鼠在训练后立即给予氯胺酮麻醉（125 毫克/公斤），但没有延迟，在抑制性回避任务中表现出增强的 48 小时记忆保留，并且这些影响被肾上腺髓质切除术、蓝斑病灶、全身或基底外侧杏仁核β-肾上腺素能受体拮抗作用。因此，氯胺酮麻醉的记忆增强作用是时间依赖性的，并由外周-中枢拟交感神经作用的组合介导。我们阐明了氯胺酮加剧急性创伤后反应的机制，可能导致生命后期出现 PTSD 症状。