Ribeiro Patrícia O, Rodrigues Paula C, Valentim Ana M, Antunes Luís M
Laboratory Animal Science, Institute for Molecular and Cell Biology, University of Porto, Porto, Portugal.
Eur J Anaesthesiol. 2013 Oct;30(10):618-26. doi: 10.1097/EJA.0b013e3283610321.
Ketamine is an anaesthetic and analgesic drug used in research and clinical practice. Little is known about the effects of different doses of this drug on memory and brain cellular death.
To study the effects of different doses of ketamine on working and reference memory, and neurodegeneration in adult mice.
A randomised study.
The study was carried out in a basic science laboratory, between March 2011 and August 2012.
Forty-eight 7-month-old, male C57BL/6 mice were used.
Animals received a single intraperitoneal injection of physiological saline solution or one of three doses of ketamine (25, 75 or 150 mg kg(-1)). Each group consisted of 12 animals (seven animals for behavioural tests and five animals for histopathological and immunohistochemical studies). The animals used for histopathology studies were sacrificed 3 h after anaesthesia.
Working and reference memories were assessed using the radial-maze test over 12 consecutive days. The equilibrium was tested using the vertical pole (4 and 24 h after injection), whereas locomotion was assessed using the open field (24, 48 and 72 h after injection). Histopathological (haematoxylin-eosin staining) and immunohistochemical analyses (procaspase-3 and activated caspase-3 detections) were performed 3 h after injection to assess neurodegeneration in the retrosplenial and visual cortices, pyramidal cell layer of the cornu Ammonis 1 and cornu Ammonis 3 areas of the hippocampus, in the granular layer of the dentate gyrus, in the laterodorsal thalamic nucleus, striatum and accumbens nucleus.
No significant differences were observed between the groups regarding the number of dead cells and cells showing positive immune-reactivity in the different regions of the brain studied. The performance in the vertical pole test and the number of reference and working memory errors in the radial-maze were similar in all groups. Nevertheless, the animals treated with ketamine 75 mg kg(-1) were transiently more active, walking a greater total distance at a greater speed in the open field than other groups (power of 0.96).
These data indicate that a single intraperitoneal injection of ketamine at subanaesthetic and anaesthetic doses does not impair working memory, reference memory or neurodegeneration in adult mice, but an intermediate dose of ketamine produces transitory hyperlocomotion.
氯胺酮是一种用于研究和临床实践的麻醉和镇痛药物。关于不同剂量的这种药物对记忆和脑细胞死亡的影响知之甚少。
研究不同剂量氯胺酮对成年小鼠工作记忆、参考记忆和神经退行性变的影响。
一项随机研究。
该研究于2011年3月至2012年8月在基础科学实验室进行。
使用48只7个月大的雄性C57BL/6小鼠。
动物接受单次腹腔注射生理盐水或三种剂量氯胺酮（25、75或150mg/kg）之一。每组由12只动物组成（7只用于行为测试，5只用于组织病理学和免疫组织化学研究）。用于组织病理学研究的动物在麻醉后3小时处死。
连续12天使用放射状迷宫试验评估工作记忆和参考记忆。使用垂直杆试验（注射后4小时和24小时）测试平衡，而使用旷场试验（注射后24、48和72小时）评估运动能力。注射后3小时进行组织病理学（苏木精-伊红染色）和免疫组织化学分析（检测procaspase-3和活化的caspase-3），以评估脾后皮质、视觉皮质、海马齿状回颗粒层、丘脑外侧背核、纹状体和伏隔核的神经退行性变。
在所研究的大脑不同区域，各组之间在死细胞数量和显示阳性免疫反应性的细胞数量方面未观察到显著差异。垂直杆试验的表现以及放射状迷宫中参考记忆和工作记忆错误的数量在所有组中相似。然而，用75mg/kg氯胺酮治疗的动物短暂性地更活跃，在旷场中比其他组以更快的速度行走更长的总距离（效能为0.96）。
这些数据表明，单次腹腔注射亚麻醉剂量和麻醉剂量的氯胺酮不会损害成年小鼠的工作记忆、参考记忆或神经退行性变，但中等剂量的氯胺酮会产生短暂的运动亢进。
