大鼠可卡因自身給藥模型的建立以及給藥程序?qū)是蠖鹊挠绊?/H1>
發(fā)布時(shí)間：2018-05-29 21:55
本文選題：藥物成癮 + 自身給藥��； 參考：《陜西師范大學(xué)》2011年碩士論文
【摘要】：目前,毒品濫用于全世界,已成為頭等重要的社會問題和醫(yī)學(xué)問題,對于其機(jī)制的研究也方興未艾。毒品作用到機(jī)體后造成藥物成癮,主要表現(xiàn)為渴求和強(qiáng)迫性覓藥行為,在使用初期會產(chǎn)生快感或減輕痛苦,繼續(xù)使用能引起中樞神經(jīng)系統(tǒng)的適應(yīng)性變化。自身給藥實(shí)驗(yàn)是研究藥物成癮的行為學(xué)模型之一,能較好地模擬人類成癮的過程,常用的給藥模式有固定比率(FR)和漸進(jìn)比率(PR)兩種。固定比率是最基礎(chǔ)的程序模式,常用于藥物濫用的初步篩選,而漸進(jìn)比率通過判斷斷點(diǎn)的大小定量地評價(jià)藥物的強(qiáng)化效應(yīng),反映動物對藥物的渴求程度。 本研究的目的是建立大鼠可卡因自身給藥模型,并對可能影響建模過程中的因素進(jìn)行探究。實(shí)驗(yàn)采用頸部外靜脈插管滯留術(shù)將插管埋于體內(nèi),藥物通過靜脈插管注入循環(huán)系統(tǒng)；在成功建立大鼠可卡因FRl自身給藥模型基礎(chǔ)上,討論了糖水預(yù)訓(xùn)練對建模的影響,觀察了不斷增大FR值大鼠可卡因渴求度的變化和可卡因劑量改變對自身給藥實(shí)驗(yàn)的影響,并在穩(wěn)定的FR1和FR5自身給藥行為基礎(chǔ)上運(yùn)用Koob程序進(jìn)行大鼠可卡因漸進(jìn)比率自身給藥實(shí)驗(yàn),探究了將程序的步階改變?yōu)?和7的訓(xùn)練后,再進(jìn)行Koob程序訓(xùn)練和Koob修改程序后斷點(diǎn)未出現(xiàn)的原因。在建立穩(wěn)定的可卡因自身給藥模型并出現(xiàn)斷點(diǎn)后,選用A2-多肽來研究可卡因自身給藥實(shí)驗(yàn)的影響。主要結(jié)果如下： 1.頸部外靜脈插管滯留術(shù)的良好狀態(tài)是自身給藥模型建立的基礎(chǔ)和成功的關(guān)鍵,插管長度、血液凝固、感染或炎癥等均能導(dǎo)致插管維持時(shí)間較短。 2.成功建立大鼠可卡因FR1自身給藥模型：經(jīng)過11天的自身給藥訓(xùn)練,2小時(shí)內(nèi)動物注射可卡因(0.75mg/kg/inj.)次數(shù)穩(wěn)定在18-24次,可卡因組有效鼻觸次數(shù)與生理鹽水組有效鼻觸次數(shù)相比有極顯著性差異,而無效鼻觸次數(shù)隨實(shí)驗(yàn)的進(jìn)行有所下降,生理鹽水組有效鼻觸次數(shù)和無效鼻觸次數(shù)在整個(gè)實(shí)驗(yàn)進(jìn)程中沒有明顯差異。 3.自身給藥訓(xùn)練前是否進(jìn)行食物訓(xùn)練,不影響可卡因自身給藥模型建立的成功率,但是經(jīng)過食物訓(xùn)練后,能加快自身給藥模型建立的速度,有利于模型的穩(wěn)定。 4.FR值和藥物劑量對自身給藥模型均有影響。FR增大時(shí),動物的有效鼻觸次數(shù)急劇增加,而藥物注射次數(shù)比較穩(wěn)定,說明FR給藥模式可在一定程度上反映動物對藥物的渴求程度；在一定劑量范圍內(nèi),可卡因劑量較低時(shí),動物有效鼻觸次數(shù)較大,藥物注射次數(shù)增加,反之亦然。 5.斷點(diǎn)的出現(xiàn)與訓(xùn)練程序有密切關(guān)系。采用Koob程序作為漸進(jìn)比率給藥模式,動物的藥物注射次數(shù)基本穩(wěn)定在20-25次,遠(yuǎn)遠(yuǎn)小于FR5的藥物注射次數(shù),而有效鼻觸次數(shù)陡然增大,大約在500-700之間,動物對藥物的需求沒有得到滿足,在實(shí)驗(yàn)第三天斷點(diǎn)出現(xiàn)。先期經(jīng)過步階為3和7的訓(xùn)練后再進(jìn)行Koob程序訓(xùn)練,未發(fā)現(xiàn)斷點(diǎn)；隨后又用兩種Koob的修改程序訓(xùn)練,仍未觀察到斷點(diǎn),表明實(shí)驗(yàn)動物經(jīng)過先期簡單的程序訓(xùn)練后,不易于觀察斷點(diǎn),究其原因可能因?yàn)樵撚?xùn)練過程中程序設(shè)定先易后難,動物在訓(xùn)練過程中始終未產(chǎn)生失望感,從未放棄通過碰觸鼻觸器來獲取藥物,還可能因?yàn)殚L期注射可卡因產(chǎn)生強(qiáng)迫性覓藥行為,動物對藥物的渴求程度較強(qiáng),強(qiáng)烈的用藥欲望驅(qū)使動物為獲得藥物而不斷碰觸鼻觸器。 6.A2-多肽對可卡因成癮的獎賞過程無影響。
[Abstract]:At present, drug abuse has become the most important social and medical problem in the world, and the research on its mechanism is also in the ascendant. Drug addiction to the body causes drug addiction, mainly as craving and compulsive drug seeking behavior. At the early stage of use, it will produce pleasure or alleviate pain and continue to use to cause the central nervous system. Adaptive change. Self administration experiment is one of the behavioral models for drug addiction. It can simulate the process of human addiction better. The commonly used mode of drug delivery has two kinds: fixed ratio (FR) and progressive ratio (PR). The fixed ratio is the most basic program mode, which is commonly used in the preliminary screening of drug abuse, and the gradual ratio is determined by the judgment of breakpoints. The size of the drug was evaluated quantitatively, reflecting the animal's craving for drugs.
The purpose of this study is to establish a model of cocaine self administration in rats and to explore the factors that may affect the process of modeling. The experiment was carried out by inserting the cannula in the body, and the drug was injected into the circulation system through the vein intubation, and on the basis of the successful establishment of the rat cocaine FRl self-administration model, the sugar was discussed. The influence of water pre training on the modeling was observed, and the influence of cocaine craving and cocaine dose change on FR value in rats was observed. On the basis of stable FR1 and FR5 self delivery behavior, Koob program was used to carry out the experiment of cocaine gradual ratio in rats, and the step change of the program was explored. After training for 3 and 7, the reasons for the failure of the Koob program and the Koob modification procedure were carried out. After establishing a stable cocaine self delivery model and breaking point, the effect of A2- polypeptide was selected to study the effect of cocaine self administration. The main results were as follows:
1. the good condition of the external jugular vein catheterization is the basis and the key to the success of the model. The length of the intubation, the blood coagulation, the infection or the inflammation can lead to the shorter duration of the intubation.
2. the rat model of cocaine FR1 was successfully established: after 11 days of self administration training, the number of cocaine injection (0.75mg/kg/inj.) was stable in 18-24 times within 2 hours. The number of effective nasal contact of cocaine group was significantly different from that of the saline group, but the number of ineffective nasal contact was lower with the experiment. The effective nasal contact times and ineffective nasal contact times in saline group were not significantly different in the whole experimental process.
3. whether or not food training before training does not affect the success rate of cocaine self feeding model, but after food training, it can speed up the establishment of the model of its own drug delivery system and be conducive to the stability of the model.
When the value of 4.FR and drug dose affect the model of self administration, the number of effective nasal contact increases sharply, and the number of drug injection is more stable. It shows that the mode of FR administration can reflect the degree of animal thirst for drugs to some extent. When the dose of cocaine is low, the number of effective nasal contact of the animals is more than that of the cocaine in a certain dose range. Big, the number of drug injection increases, and vice versa.
The occurrence of 5. breakpoints is closely related to the training program. Using the Koob program as a progressive ratio drug delivery mode, the number of injections of animals is basically stable at 20-25 times, far less than the number of injection of FR5, and the number of effective nasal contact increases abruptly, about 500-700, the demand for drugs has not been met, in experiment third Koob program training after the step of 3 and 7 training, no breakpoint was found, and then two Koob modification programs were used, and the breakpoints were still not observed. It showed that the experimental animals were not easy to observe the breakpoints after the first simple program training. The reason may be that the program was set first in the training process. It is difficult for the animals to feel disappointing during the training process and never give up the drug by touching the nose touch device. It may also result from the long injection of cocaine to produce compulsive drug seeking behavior, the animal thirst for drugs is stronger, and the strong desire for drug use drives the animals to touch the nose touch continuously.
6.A2- peptide has no effect on the reward process of cocaine addiction.
【學(xué)位授予單位】：陜西師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R749.6;R-332
【共引文獻(xiàn)】
相關(guān)期刊論文 前7條
1 侯媛媛;劉志強(qiáng);張星星;錢召強(qiáng);張遐;;條件位置偏愛實(shí)驗(yàn)和自身給藥實(shí)驗(yàn)及其比較[J];現(xiàn)代生物醫(yī)學(xué)進(jìn)展;2011年S2期
2 肖健,姜長青;嗎啡成癮的大鼠行為改變及其與腦內(nèi)單胺類神經(jīng)介質(zhì)含量變化的關(guān)系[J];心理學(xué)報(bào);1983年04期
3 陶青;;評價(jià)藥物精神依賴性的方法——動物自身給藥實(shí)驗(yàn)[J];中國藥物依賴性通報(bào);1990年02期
4 呂秀依;翟海峰;馬寶苗;劉昱;;藥物靜脈自身給藥發(fā)展和藥物強(qiáng)化作用認(rèn)同的歷史沿革[J];中國藥物依賴性雜志;2011年01期
5 趙春;張栗;馬寶苗;呂秀依;吳瑋;孫艷;劉昱;;累進(jìn)比率在自身給藥模型中的應(yīng)用[J];中國藥物依賴性雜志;2011年03期
6 李俊旭;;行為藥理學(xué):歷史與現(xiàn)狀[J];神經(jīng)藥理學(xué)報(bào);2011年01期
7 岳衛(wèi)清;曹明;姚明榮;;帕羅西汀治療酒依賴臨床療效研究[J];中國藥物濫用防治雜志;2010年06期
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本文編號：1952558
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本文選題：藥物成癮 + 自身給藥��； 參考：《陜西師范大學(xué)》2011年碩士論文
【摘要】：目前,毒品濫用于全世界,已成為頭等重要的社會問題和醫(yī)學(xué)問題,對于其機(jī)制的研究也方興未艾。毒品作用到機(jī)體后造成藥物成癮,主要表現(xiàn)為渴求和強(qiáng)迫性覓藥行為,在使用初期會產(chǎn)生快感或減輕痛苦,繼續(xù)使用能引起中樞神經(jīng)系統(tǒng)的適應(yīng)性變化。自身給藥實(shí)驗(yàn)是研究藥物成癮的行為學(xué)模型之一,能較好地模擬人類成癮的過程,常用的給藥模式有固定比率(FR)和漸進(jìn)比率(PR)兩種。固定比率是最基礎(chǔ)的程序模式,常用于藥物濫用的初步篩選,而漸進(jìn)比率通過判斷斷點(diǎn)的大小定量地評價(jià)藥物的強(qiáng)化效應(yīng),反映動物對藥物的渴求程度。 本研究的目的是建立大鼠可卡因自身給藥模型,并對可能影響建模過程中的因素進(jìn)行探究。實(shí)驗(yàn)采用頸部外靜脈插管滯留術(shù)將插管埋于體內(nèi),藥物通過靜脈插管注入循環(huán)系統(tǒng)；在成功建立大鼠可卡因FRl自身給藥模型基礎(chǔ)上,討論了糖水預(yù)訓(xùn)練對建模的影響,觀察了不斷增大FR值大鼠可卡因渴求度的變化和可卡因劑量改變對自身給藥實(shí)驗(yàn)的影響,并在穩(wěn)定的FR1和FR5自身給藥行為基礎(chǔ)上運(yùn)用Koob程序進(jìn)行大鼠可卡因漸進(jìn)比率自身給藥實(shí)驗(yàn),探究了將程序的步階改變?yōu)?和7的訓(xùn)練后,再進(jìn)行Koob程序訓(xùn)練和Koob修改程序后斷點(diǎn)未出現(xiàn)的原因。在建立穩(wěn)定的可卡因自身給藥模型并出現(xiàn)斷點(diǎn)后,選用A2-多肽來研究可卡因自身給藥實(shí)驗(yàn)的影響。主要結(jié)果如下： 1.頸部外靜脈插管滯留術(shù)的良好狀態(tài)是自身給藥模型建立的基礎(chǔ)和成功的關(guān)鍵,插管長度、血液凝固、感染或炎癥等均能導(dǎo)致插管維持時(shí)間較短。 2.成功建立大鼠可卡因FR1自身給藥模型：經(jīng)過11天的自身給藥訓(xùn)練,2小時(shí)內(nèi)動物注射可卡因(0.75mg/kg/inj.)次數(shù)穩(wěn)定在18-24次,可卡因組有效鼻觸次數(shù)與生理鹽水組有效鼻觸次數(shù)相比有極顯著性差異,而無效鼻觸次數(shù)隨實(shí)驗(yàn)的進(jìn)行有所下降,生理鹽水組有效鼻觸次數(shù)和無效鼻觸次數(shù)在整個(gè)實(shí)驗(yàn)進(jìn)程中沒有明顯差異。 3.自身給藥訓(xùn)練前是否進(jìn)行食物訓(xùn)練,不影響可卡因自身給藥模型建立的成功率,但是經(jīng)過食物訓(xùn)練后,能加快自身給藥模型建立的速度,有利于模型的穩(wěn)定。 4.FR值和藥物劑量對自身給藥模型均有影響。FR增大時(shí),動物的有效鼻觸次數(shù)急劇增加,而藥物注射次數(shù)比較穩(wěn)定,說明FR給藥模式可在一定程度上反映動物對藥物的渴求程度；在一定劑量范圍內(nèi),可卡因劑量較低時(shí),動物有效鼻觸次數(shù)較大,藥物注射次數(shù)增加,反之亦然。 5.斷點(diǎn)的出現(xiàn)與訓(xùn)練程序有密切關(guān)系。采用Koob程序作為漸進(jìn)比率給藥模式,動物的藥物注射次數(shù)基本穩(wěn)定在20-25次,遠(yuǎn)遠(yuǎn)小于FR5的藥物注射次數(shù),而有效鼻觸次數(shù)陡然增大,大約在500-700之間,動物對藥物的需求沒有得到滿足,在實(shí)驗(yàn)第三天斷點(diǎn)出現(xiàn)。先期經(jīng)過步階為3和7的訓(xùn)練后再進(jìn)行Koob程序訓(xùn)練,未發(fā)現(xiàn)斷點(diǎn)；隨后又用兩種Koob的修改程序訓(xùn)練,仍未觀察到斷點(diǎn),表明實(shí)驗(yàn)動物經(jīng)過先期簡單的程序訓(xùn)練后,不易于觀察斷點(diǎn),究其原因可能因?yàn)樵撚?xùn)練過程中程序設(shè)定先易后難,動物在訓(xùn)練過程中始終未產(chǎn)生失望感,從未放棄通過碰觸鼻觸器來獲取藥物,還可能因?yàn)殚L期注射可卡因產(chǎn)生強(qiáng)迫性覓藥行為,動物對藥物的渴求程度較強(qiáng),強(qiáng)烈的用藥欲望驅(qū)使動物為獲得藥物而不斷碰觸鼻觸器。 6.A2-多肽對可卡因成癮的獎賞過程無影響。
[Abstract]:At present, drug abuse has become the most important social and medical problem in the world, and the research on its mechanism is also in the ascendant. Drug addiction to the body causes drug addiction, mainly as craving and compulsive drug seeking behavior. At the early stage of use, it will produce pleasure or alleviate pain and continue to use to cause the central nervous system. Adaptive change. Self administration experiment is one of the behavioral models for drug addiction. It can simulate the process of human addiction better. The commonly used mode of drug delivery has two kinds: fixed ratio (FR) and progressive ratio (PR). The fixed ratio is the most basic program mode, which is commonly used in the preliminary screening of drug abuse, and the gradual ratio is determined by the judgment of breakpoints. The size of the drug was evaluated quantitatively, reflecting the animal's craving for drugs.
The purpose of this study is to establish a model of cocaine self administration in rats and to explore the factors that may affect the process of modeling. The experiment was carried out by inserting the cannula in the body, and the drug was injected into the circulation system through the vein intubation, and on the basis of the successful establishment of the rat cocaine FRl self-administration model, the sugar was discussed. The influence of water pre training on the modeling was observed, and the influence of cocaine craving and cocaine dose change on FR value in rats was observed. On the basis of stable FR1 and FR5 self delivery behavior, Koob program was used to carry out the experiment of cocaine gradual ratio in rats, and the step change of the program was explored. After training for 3 and 7, the reasons for the failure of the Koob program and the Koob modification procedure were carried out. After establishing a stable cocaine self delivery model and breaking point, the effect of A2- polypeptide was selected to study the effect of cocaine self administration. The main results were as follows:
1. the good condition of the external jugular vein catheterization is the basis and the key to the success of the model. The length of the intubation, the blood coagulation, the infection or the inflammation can lead to the shorter duration of the intubation.
2. the rat model of cocaine FR1 was successfully established: after 11 days of self administration training, the number of cocaine injection (0.75mg/kg/inj.) was stable in 18-24 times within 2 hours. The number of effective nasal contact of cocaine group was significantly different from that of the saline group, but the number of ineffective nasal contact was lower with the experiment. The effective nasal contact times and ineffective nasal contact times in saline group were not significantly different in the whole experimental process.
3. whether or not food training before training does not affect the success rate of cocaine self feeding model, but after food training, it can speed up the establishment of the model of its own drug delivery system and be conducive to the stability of the model.
When the value of 4.FR and drug dose affect the model of self administration, the number of effective nasal contact increases sharply, and the number of drug injection is more stable. It shows that the mode of FR administration can reflect the degree of animal thirst for drugs to some extent. When the dose of cocaine is low, the number of effective nasal contact of the animals is more than that of the cocaine in a certain dose range. Big, the number of drug injection increases, and vice versa.
The occurrence of 5. breakpoints is closely related to the training program. Using the Koob program as a progressive ratio drug delivery mode, the number of injections of animals is basically stable at 20-25 times, far less than the number of injection of FR5, and the number of effective nasal contact increases abruptly, about 500-700, the demand for drugs has not been met, in experiment third Koob program training after the step of 3 and 7 training, no breakpoint was found, and then two Koob modification programs were used, and the breakpoints were still not observed. It showed that the experimental animals were not easy to observe the breakpoints after the first simple program training. The reason may be that the program was set first in the training process. It is difficult for the animals to feel disappointing during the training process and never give up the drug by touching the nose touch device. It may also result from the long injection of cocaine to produce compulsive drug seeking behavior, the animal thirst for drugs is stronger, and the strong desire for drug use drives the animals to touch the nose touch continuously.
6.A2- peptide has no effect on the reward process of cocaine addiction.
【學(xué)位授予單位】：陜西師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R749.6;R-332
【共引文獻(xiàn)】
相關(guān)期刊論文 前7條
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5 趙春;張栗;馬寶苗;呂秀依;吳瑋;孫艷;劉昱;;累進(jìn)比率在自身給藥模型中的應(yīng)用[J];中國藥物依賴性雜志;2011年03期
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7 岳衛(wèi)清;曹明;姚明榮;;帕羅西汀治療酒依賴臨床療效研究[J];中國藥物濫用防治雜志;2010年06期
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