大鼠可卡因自身给药模型的建立以及给药程序对渴求度的影响

发布时间：2018-05-29 21:55

本文选题：药物成瘾 + 自身给药　；参考：《陕西师范大学》2011年硕士论文

【摘要】：目前,毒品滥用于全世界,已成为头等重要的社会问题和医学问题,对于其机制的研究也方兴未艾。毒品作用到机体后造成药物成瘾,主要表现为渴求和强迫性觅药行为,在使用初期会产生快感或减轻痛苦,继续使用能引起中枢神经系统的适应性变化。自身给药实验是研究药物成瘾的行为学模型之一,能较好地模拟人类成瘾的过程,常用的给药模式有固定比率(FR)和渐进比率(PR)两种。固定比率是最基础的程序模式,常用于药物滥用的初步筛选,而渐进比率通过判断断点的大小定量地评价药物的强化效应,反映动物对药物的渴求程度。本研究的目的是建立大鼠可卡因自身给药模型,并对可能影响建模过程中的因素进行探究。实验采用颈部外静脉插管滞留术将插管埋于体内,药物通过静脉插管注入循环系统；在成功建立大鼠可卡因FRl自身给药模型基础上,讨论了糖水预训练对建模的影响,观察了不断增大FR值大鼠可卡因渴求度的变化和可卡因剂量改变对自身给药实验的影响,并在稳定的FR1和FR5自身给药行为基础上运用Koob程序进行大鼠可卡因渐进比率自身给药实验,探究了将程序的步阶改变为3和7的训练后,再进行Koob程序训练和Koob修改程序后断点未出现的原因。在建立稳定的可卡因自身给药模型并出现断点后,选用A2-多肽来研究可卡因自身给药实验的影响。主要结果如下： 1.颈部外静脉插管滞留术的良好状态是自身给药模型建立的基础和成功的关键,插管长度、血液凝固、感染或炎症等均能导致插管维持时间较短。 2.成功建立大鼠可卡因FR1自身给药模型：经过11天的自身给药训练,2小时内动物注射可卡因(0.75mg/kg/inj.)次数稳定在18-24次,可卡因组有效鼻触次数与生理盐水组有效鼻触次数相比有极显著性差异,而无效鼻触次数随实验的进行有所下降,生理盐水组有效鼻触次数和无效鼻触次数在整个实验进程中没有明显差异。 3.自身给药训练前是否进行食物训练,不影响可卡因自身给药模型建立的成功率,但是经过食物训练后,能加快自身给药模型建立的速度,有利于模型的稳定。 4.FR值和药物剂量对自身给药模型均有影响。FR增大时,动物的有效鼻触次数急剧增加,而药物注射次数比较稳定,说明FR给药模式可在一定程度上反映动物对药物的渴求程度；在一定剂量范围内,可卡因剂量较低时,动物有效鼻触次数较大,药物注射次数增加,反之亦然。 5.断点的出现与训练程序有密切关系。采用Koob程序作为渐进比率给药模式,动物的药物注射次数基本稳定在20-25次,远远小于FR5的药物注射次数,而有效鼻触次数陡然增大,大约在500-700之间,动物对药物的需求没有得到满足,在实验第三天断点出现。先期经过步阶为3和7的训练后再进行Koob程序训练,未发现断点；随后又用两种Koob的修改程序训练,仍未观察到断点,表明实验动物经过先期简单的程序训练后,不易于观察断点,究其原因可能因为该训练过程中程序设定先易后难,动物在训练过程中始终未产生失望感,从未放弃通过碰触鼻触器来获取药物,还可能因为长期注射可卡因产生强迫性觅药行为,动物对药物的渴求程度较强,强烈的用药欲望驱使动物为获得药物而不断碰触鼻触器。 6.A2-多肽对可卡因成瘾的奖赏过程无影响。
[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.
【学位授予单位】：陕西师范大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R749.6;R-332

【共引文献】