运动应激对氯胺酮成瘾相关行为的影响

发布时间：2018-08-17 10:35

【摘要】：目的：氯胺酮是一种分离性麻醉药,在临床上被用作手术麻醉剂或麻醉诱导剂，具有一定的镇痛作用，，长期服用会出现致幻作用与成瘾性。有关氯胺酮成瘾的研究有很多，但运动应激对氯胺酮成瘾是否产生影响未见报道，本研究：1）通过条件性位置偏爱实验观测小鼠氯胺酮的奖赏特征；2）采用动物跑台试验观测运动应激干预对小鼠成瘾行为的影响；3）通过自发活动、高架十字迷宫、强迫游泳和悬尾等实验，观测长期给予氯胺酮对小鼠抑郁焦虑行为的影响。方法：条件性位置偏爱（CPP）实验，首先对ICR小鼠进行CPP初测，根据结果将小鼠分为对照组、1mg/kg氯胺酮、3mg/kg氯胺酮和10mg/kg氯胺酮四组，给药方式为腹腔给药，然后进行8天CPP训练，训练时间为上午8:00和下午16:00，第9天进行CPP值测试。根据以上实验我们选用剂量为10mg/kg进行小鼠CPP训练，训练时间同上，在中午12:00时进行跑台实验。小鼠焦虑与抑郁实验，首先对ICR小鼠进行分组，分为对照组（生理盐水）、氯胺酮5mg/kg、氯胺酮10mg/kg、氯胺酮20mg/kg四组，给药时间和给药方式同上，第九天分别对小鼠进行自发活动、焦虑行为（高架十字迷宫实验）抑郁行为（悬尾实验、强迫游泳实验）测试。结果：小鼠CPP实验中，氯胺酮（1mg/kg、3mg/kg、10mg/kg）三个剂量的小鼠CPP值高于对照组（P0.05）；在小鼠CPP训练时加入运动干预，运动干预后小鼠CPP值要低于氯胺酮组（P0.05）；自发活动实验中，对照组与氯胺酮高、中、低三个剂量组相比较，三个剂量对小鼠自发活动与探究行为有增加趋势（P0.05）；高架十字迷宫实实验中，对照组氯胺酮高、中、低三个剂量组与对照组相比较，中、高剂量对小鼠在开放臂时间（OE）（P0.05）与穿梭次数（OT）（P0.05）有增加趋势，与低剂量组相比较无差异；在悬尾实验中，对照组与氯胺酮高、中、低三个剂量相比较，三个剂量的小鼠比对照组悬挂时不动时间要短（P0.05）；小鼠强迫游泳实验中，对照组与氯胺酮高、中、低三个剂量相啊比较，三个剂量的小鼠在水中不动时间都有延长趋势（P0.05）。结论：在鼠条件性位置偏爱实验中，加入运动干预可以抑制小鼠的CPP表达；长期给予氯胺酮对增加小鼠自发活动有一定趋势；长期给予氯胺酮能够对小鼠起到抗抑焦虑、抑郁行为。
[Abstract]:OBJECTIVE: Ketamine is a kind of separated anesthetic, which is used as anesthetic or anesthetic inducer for surgery in clinic. It has certain analgesic effect and has hallucinogenic effect and addiction after long-term administration. There are many studies on ketamine addiction, but there is no report on the effect of exercise stress on ketamine addiction. Conditional place preference test was used to observe the reward characteristics of ketamine in mice; 2) animal treadmill test was used to observe the effects of exercise stress intervention on addictive behavior in mice; 3) The effects of long-term ketamine administration on depression and anxiety behavior in mice were observed through spontaneous activities, elevated maze, forced swimming and tail suspension experiments.
METHODS: Conditional place preference (CPP) test was conducted in ICR mice. According to the results, the mice were divided into four groups: control group, 1 mg/kg ketamine, 3 mg/kg ketamine and 10 mg/kg ketamine. The mice were administered intraperitoneally and then trained for 8 days. The training time was 8:00 a.m. and 16:00 p.m., and the CPP value was tested on the 9th day. In the last experiment, we used the dosage of 10 mg/kg to train CPP in mice. The training time was the same. The treadmill experiment was carried out at 12:00 noon.
Anxiety and depression test in mice, ICR mice were divided into four groups: control group (normal saline), ketamine 5 mg/kg, ketamine 10 mg/kg, ketamine 20 mg/kg. The administration time and manner were the same. On the ninth day, the mice were given spontaneous activity, anxiety behavior (elevated cross maze test) depression behavior (tail suspension test, forced swimming). Experiment) test.
Results: In the CPP test, the CPP value of the mice with ketamine (1 mg/kg, 3 mg/kg, 10 mg/kg) was higher than that of the control group (P 0.05); the CPP value of the mice with exercise intervention was lower than that of the ketamine group (P 0.05); in the spontaneous activity test, the control group was compared with the high, middle and low dose ketamine groups, and the three doses of ketamine, respectively. The spontaneous activity and exploratory behavior of mice increased with dosage (P 0.05); in the elevated maze experiment, the control group with high, medium and low doses of ketamine compared with the control group, the open arm time (OE) (P 0.05) and shuttle times (OT) (P 0.05) of mice increased with the high dose group, compared with the low dose group, there was no difference in tail suspension. In the experiment, the immobility time of mice in the control group was shorter than that in the control group (P 0.05), and the immobility time of mice in the three doses was longer than that in the control group (P 0.05).
CONCLUSION: In conditioned place preference test, exercise intervention can inhibit the expression of CPP in mice; long-term ketamine administration has a certain tendency to increase spontaneous activity in mice; long-term ketamine administration can inhibit anxiety and depressive behavior in mice.
【学位授予单位】：中北大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R749.6

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