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運(yùn)動(dòng)應(yīng)激對(duì)氯胺酮成癮相關(guān)行為的影響

發(fā)布時(shí)間:2018-08-17 10:35
【摘要】:目的:氯胺酮是一種分離性麻醉藥,在臨床上被用作手術(shù)麻醉劑或麻醉誘導(dǎo)劑,具有一定的鎮(zhèn)痛作用,,長(zhǎng)期服用會(huì)出現(xiàn)致幻作用與成癮性。有關(guān)氯胺酮成癮的研究有很多,但運(yùn)動(dòng)應(yīng)激對(duì)氯胺酮成癮是否產(chǎn)生影響未見(jiàn)報(bào)道,本研究:1)通過(guò)條件性位置偏愛(ài)實(shí)驗(yàn)觀測(cè)小鼠氯胺酮的獎(jiǎng)賞特征;2)采用動(dòng)物跑臺(tái)試驗(yàn)觀測(cè)運(yùn)動(dòng)應(yīng)激干預(yù)對(duì)小鼠成癮行為的影響;3)通過(guò)自發(fā)活動(dòng)、高架十字迷宮、強(qiáng)迫游泳和懸尾等實(shí)驗(yàn),觀測(cè)長(zhǎng)期給予氯胺酮對(duì)小鼠抑郁焦慮行為的影響。 方法:條件性位置偏愛(ài)(CPP)實(shí)驗(yàn),首先對(duì)ICR小鼠進(jìn)行CPP初測(cè),根據(jù)結(jié)果將小鼠分為對(duì)照組、1mg/kg氯胺酮、3mg/kg氯胺酮和10mg/kg氯胺酮四組,給藥方式為腹腔給藥,然后進(jìn)行8天CPP訓(xùn)練,訓(xùn)練時(shí)間為上午8:00和下午16:00,第9天進(jìn)行CPP值測(cè)試。根據(jù)以上實(shí)驗(yàn)我們選用劑量為10mg/kg進(jìn)行小鼠CPP訓(xùn)練,訓(xùn)練時(shí)間同上,在中午12:00時(shí)進(jìn)行跑臺(tái)實(shí)驗(yàn)。 小鼠焦慮與抑郁實(shí)驗(yàn),首先對(duì)ICR小鼠進(jìn)行分組,分為對(duì)照組(生理鹽水)、氯胺酮5mg/kg、氯胺酮10mg/kg、氯胺酮20mg/kg四組,給藥時(shí)間和給藥方式同上,第九天分別對(duì)小鼠進(jìn)行自發(fā)活動(dòng)、焦慮行為(高架十字迷宮實(shí)驗(yàn))抑郁行為(懸尾實(shí)驗(yàn)、強(qiáng)迫游泳實(shí)驗(yàn))測(cè)試。 結(jié)果:小鼠CPP實(shí)驗(yàn)中,氯胺酮(1mg/kg、3mg/kg、10mg/kg)三個(gè)劑量的小鼠CPP值高于對(duì)照組(P0.05);在小鼠CPP訓(xùn)練時(shí)加入運(yùn)動(dòng)干預(yù),運(yùn)動(dòng)干預(yù)后小鼠CPP值要低于氯胺酮組(P0.05);自發(fā)活動(dòng)實(shí)驗(yàn)中,對(duì)照組與氯胺酮高、中、低三個(gè)劑量組相比較,三個(gè)劑量對(duì)小鼠自發(fā)活動(dòng)與探究行為有增加趨勢(shì)(P0.05);高架十字迷宮實(shí)實(shí)驗(yàn)中,對(duì)照組氯胺酮高、中、低三個(gè)劑量組與對(duì)照組相比較,中、高劑量對(duì)小鼠在開(kāi)放臂時(shí)間(OE)(P0.05)與穿梭次數(shù)(OT)(P0.05)有增加趨勢(shì),與低劑量組相比較無(wú)差異;在懸尾實(shí)驗(yàn)中,對(duì)照組與氯胺酮高、中、低三個(gè)劑量相比較,三個(gè)劑量的小鼠比對(duì)照組懸掛時(shí)不動(dòng)時(shí)間要短(P0.05);小鼠強(qiáng)迫游泳實(shí)驗(yàn)中,對(duì)照組與氯胺酮高、中、低三個(gè)劑量相啊比較,三個(gè)劑量的小鼠在水中不動(dòng)時(shí)間都有延長(zhǎng)趨勢(shì)(P0.05)。 結(jié)論:在鼠條件性位置偏愛(ài)實(shí)驗(yàn)中,加入運(yùn)動(dòng)干預(yù)可以抑制小鼠的CPP表達(dá);長(zhǎng)期給予氯胺酮對(duì)增加小鼠自發(fā)活動(dòng)有一定趨勢(shì);長(zhǎng)期給予氯胺酮能夠?qū)π∈笃鸬娇挂纸箲]、抑郁行為。
[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.
【學(xué)位授予單位】:中北大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2014
【分類號(hào)】:R749.6

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