Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Anaesthesia, Harvard Medical School, Boston, MA, USA.
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Anaesthesia, Harvard Medical School, Boston, MA, USA.
Br J Anaesth. 2024 Oct;133(4):793-803. doi: 10.1016/j.bja.2024.05.026. Epub 2024 Jul 3.
Dopaminergic psychostimulants can restore arousal in anaesthetised animals, and dopaminergic signalling contributes to hippocampal-dependent memory formation. We tested the hypothesis that dopaminergic psychostimulants can antagonise the amnestic effects of isoflurane on visuospatial working memory.
Sixteen adult Sprague-Dawley rats were trained on a trial-unique nonmatching-to-location (TUNL) task which assessed the ability to identify a novel touchscreen location after a fixed delay. Once trained, the effects of low-dose isoflurane (0.3 vol%) on task performance and activity, assessed by infrared beam breaks, were assessed. We attempted to rescue deficits in performance and activity with a dopamine D1 receptor agonist (chloro-APB), a noradrenergic reuptake inhibitor (atomoxetine), and a mixed dopamine/norepinephrine releasing agent (dextroamphetamine). Anaesthetic induction, emergence, and recovery from anaesthesia were also investigated.
Low-dose isoflurane impaired working memory in a sex-independent and intra-trial delay-independent manner as assessed by task performance, and caused an overall reduction in activity. Administration of chloro-APB, atomoxetine, or dextroamphetamine did not restore visuospatial working memory, but chloro-APB and dextroamphetamine recovered arousal to levels observed in the baseline awake state. Performance did not differ between induction and emergence. Animals recovered to baseline performance within 15 min of discontinuing isoflurane.
Low-dose isoflurane impairs visuospatial working memory in a nondurable and delay-independent manner that potentially implicates non-hippocampal structures in isoflurane-induced memory deficits. Dopaminergic psychostimulants counteracted sedation but did not reverse memory impairments, suggesting that isoflurane-induced amnesia and isoflurane-induced sedation have distinct underlying mechanisms that can be antagonised independently.
多巴胺能精神兴奋剂可恢复麻醉动物的觉醒，而多巴胺能信号传导有助于海马依赖性记忆形成。我们检验了这样一个假设，即多巴胺能精神兴奋剂可拮抗异氟醚对视觉空间工作记忆的健忘作用。
16 只成年 Sprague-Dawley 大鼠接受了独特试验非匹配定位（TUNL）任务的训练，该任务评估了在固定延迟后识别新触摸屏位置的能力。一旦训练完成，就评估了低剂量异氟醚（0.3 体积%）对任务表现和活动的影响，通过红外光束中断进行评估。我们试图用多巴胺 D1 受体激动剂（氯-APB）、去甲肾上腺素再摄取抑制剂（阿托西汀）和混合多巴胺/去甲肾上腺素释放剂（右旋苯丙胺）来挽救表现和活动的缺陷。还研究了麻醉诱导、苏醒和麻醉恢复。
低剂量异氟醚以性别独立和试验内延迟独立的方式损害工作记忆，表现为任务表现受损，并导致整体活动减少。氯-APB、阿托西汀或右旋苯丙胺的给药并未恢复视觉空间工作记忆，但氯-APB 和右旋苯丙胺恢复了觉醒，达到了基础清醒状态下观察到的水平。诱导和苏醒之间的性能没有差异。动物在停止异氟醚 15 分钟内恢复到基线性能。
低剂量异氟醚以非持久和延迟独立的方式损害视觉空间工作记忆，这可能暗示非海马结构参与了异氟醚引起的记忆缺陷。多巴胺能精神兴奋剂拮抗镇静作用，但未逆转记忆损伤，这表明异氟醚引起的健忘症和异氟醚引起的镇静作用具有不同的潜在机制，可以独立拮抗。
