单次氯胺酮注射对孕鼠子代认知功能的研究

The effects of ketamine on learning and memory function in the pregnant rat＇ s offspring

目的探讨单次氯胺酮注射对孕鼠子代在空间认知能力、探索能力方面的行为学改变。方法3月龄SD同胞雌大鼠12对，用随机数字表法分为4组（n=6）：对照组（N），小剂量氯胺酮组（K1），临床麻醉剂量氯胺酮组（K2），大剂量氯胺酮组（I（3），与同龄SD同胞雄鼠4只按雌雄比例2：1同笼交配受孕。K1、K2、K3组在孕鼠敏感致畸期（6—15d）的第10天分别以3，8，20mg／kg行尾静脉单次注射氯胺酮，N组单次注射生理盐水2ml。在孕鼠子代20d时进行旷场实验测试（记录新生大鼠在中央格停留时间（S）和2rain内穿越的格子数）和洞板实验（计数5min内大鼠伸入洞的次数）。结果旷场试验中，N、K2、K3组中央格停留时间分别是（2．45±1．23）S，（6．42±2．50）S，（6．41±2．19）s。与N组比较，K2组和K3组新生大鼠在中央格停留的时间明显高（F=13．42，P〈0．01），K1组无明显增高[（3．27±1．74）S，t=1．33，P〉0．05）]。K1、K2、K3组穿越格子数减少[（15．33±6．81）个，（13．75±5．93）个，（16．92±6．54）个，F=4．24]，差异有显著性（P〈0．05）。洞板试验中，各组间比较，孕鼠子代的探洞次数差异无显著性（F=2．17，P〉0．01）。结论相当于临床麻醉剂量的氯胺酮单次静脉注射能影响孕鼠子代的空间认知能力；但对其探索认知能力无明显影响。

Objective To investigate whether pregnant rats exposure to ketamine cause offspring changes in space cognitive abilities and exploration abilities. Methods 3-month Sprague-Dawley female rats （ n = 24 ） were randomly divided into four groups： group N （control group）, group K1 （small doses of ketamine group）, group K2 （clinical anesthesia dose of ketamine group） , group K3 （large doses of ketamine group）. 3-month Sprague-Dawley male rats （ n =4） and female rats were mated at the same cage by the proportion of 2： 1. Pregnant mice were treated at tenth day： group N were treated saline with equal-volume to ketamine vein injection;group K1 ,group K2, group K3 administered vein injection 3,8,20mg/kg of ketamine. Then the 20-day offspring rats＂ learning and memory were assessed used Open Field Test （ record the time of the offspring in the central case through the number of grid within 2 min ） and Hole Board Test （ Counting the times of offspring stretch into the hole in 5 min） at postnatal days 20. Results In the Open Field Test, the retention time in central check of group N,group K2 and group K3 were （2.45 ± 1.23）s,（6.42 ±2.50）s,（6.41 ±2.19）s. Compared with group N,the retention time in central check of group K2 and group K3 were significantly higher （F= 13.42 , P〈0.01 ） , and group K1 were not significant different （ t= 1.33, P〉0.01 ） ,and the locomotion of group K1 ,group K2,group K3 were significantly reduced（ （ 15.33 ± 6.81 ）, （ 13.75± 5.93 ）, （ 16.92 ± 6.54）, F = 4.24, P 〈 0.05 ）. In the Hole Board Test, the times of offspring stretch into the hole were not significant different comparing with the control group（F = 2.17, P 〉 0.05 ）. Conclusion The dose of ketamine that equivalented clinical anesthesia can affect offspring rats＇ space cognitive abilities; but the exploring cognitive ability were not significantly influenced.