Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：多巴胺能精神兴奋剂可以恢复麻醉动物的唤醒，多巴胺能信号传导有助于海马依赖性记忆形成。我们测试了多巴胺能精神兴奋剂可以拮抗异氟烷对视空间工作记忆的遗忘作用的假设。
方法：对16只成年Sprague-Dawley大鼠进行了一项独特的试验非位置匹配（TUNL）任务，该任务评估了在固定延迟后识别新触摸屏位置的能力。一旦受过训练，低剂量异氟烷（0.3vol%）对任务表现和活动的影响，通过红外光束中断来评估，被评估。我们试图用多巴胺D1受体激动剂（氯-APB）挽救性能和活性的缺陷，去甲肾上腺素能再摄取抑制剂（托莫西汀），和混合的多巴胺/去甲肾上腺素释放剂（右旋苯丙胺）。麻醉诱导,出现，并对麻醉恢复情况进行了调查。
结果：低剂量异氟烷以性别独立和试验内延迟独立的方式损害工作记忆，通过任务表现评估，并导致活动整体减少。氯APB的管理，托莫西汀,或者右旋苯丙胺不能恢复视觉空间工作记忆，但是氯-APB和右苯丙胺恢复了在基线清醒状态下观察到的唤醒水平.诱导和出现之间的性能没有差异。动物在停止异氟烷的15分钟内恢复到基线性能。
结论：低剂量异氟烷以非持久和延迟无关的方式损害视觉空间工作记忆，这可能与异氟烷诱导的记忆缺陷有关非海马结构。多巴胺能精神兴奋剂可以抵消镇静作用，但不能逆转记忆障碍，提示异氟烷诱导的健忘症和异氟烷诱导的镇静具有不同的潜在机制，可以独立拮抗。
方法：对16只成年Sprague-Dawley大鼠进行了一项独特的试验非位置匹配（TUNL）任务，该任务评估了在固定延迟后识别新触摸屏位置的能力。一旦受过训练，低剂量异氟烷（0.3vol%）对任务表现和活动的影响，通过红外光束中断来评估，被评估。我们试图用多巴胺D1受体激动剂（氯-APB）挽救性能和活性的缺陷，去甲肾上腺素能再摄取抑制剂（托莫西汀），和混合的多巴胺/去甲肾上腺素释放剂（右旋苯丙胺）。麻醉诱导,出现，并对麻醉恢复情况进行了调查。
结果：低剂量异氟烷以性别独立和试验内延迟独立的方式损害工作记忆，通过任务表现评估，并导致活动整体减少。氯APB的管理，托莫西汀,或者右旋苯丙胺不能恢复视觉空间工作记忆，但是氯-APB和右苯丙胺恢复了在基线清醒状态下观察到的唤醒水平.诱导和出现之间的性能没有差异。动物在停止异氟烷的15分钟内恢复到基线性能。
结论：低剂量异氟烷以非持久和延迟无关的方式损害视觉空间工作记忆，这可能与异氟烷诱导的记忆缺陷有关非海马结构。多巴胺能精神兴奋剂可以抵消镇静作用，但不能逆转记忆障碍，提示异氟烷诱导的健忘症和异氟烷诱导的镇静具有不同的潜在机制，可以独立拮抗。
