大鼠可卡因自身给药消退—恢复模型的建立及人工合成Tat-A2对复吸的影响

发布时间：2018-01-03 05:45

本文关键词：大鼠可卡因自身给药消退—恢复模型的建立及人工合成Tat-A2对复吸的影响　出处：《陕西师范大学》2012年硕士论文　论文类型：学位论文

【摘要】：药物成瘾是以失去控制能力、强迫性连续用药为主要特征的慢性复发性复杂脑疾病,是由生物、行为和环境因素共同作用引起。在对其长期的治疗和研究中发现,难以克制的复吸是其典型的表现形式。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；在产生依赖后,一旦撒药就会产生戒断等不适症状。自身给药消退(extinction)-恢复(reinstatement)模型是当今公认的研究药物成瘾后复吸的行为学模型之一,能较好地模拟人类成瘾发生、发展中的不同阶段,包括静脉自身给药行为、自身给药消退、药物直接引燃/自身给药环境诱导/应激诱导的恢复阶段。该模型的建立一般采用固定比率为1(FR1)的给药模式建立自身给药模型,然后进行自身给药行为的消退,最后进行自身给药行为恢复测试。本研究的目的包括：建立大鼠可卡因自身给药消退-恢复模型,并对建模进行讨论；检测一种人工合成的LTP阻断肽——Tat-A2,对于可卡因直接引燃的觅药行为恢复的作用,并对结果进行讨论。主要实验结果如下 (1)自身给药模型建立的基础和成功的关键是颈部外静脉插管滞留术及维持,手术操作、插管长度、术后插管通畅程度、感染或炎症等均能影响插管维持时间。 (2)大鼠可卡因FRl自身给药成瘾行为的成功建立。经过6天的人为辅助和14天的大鼠自身给药行为训练,每天2小时训练时期内动物注射可卡因(0.75mg/kg/inj.)次数逐步升高并稳定在33.17±1.45次,而无效鼻触次数伴随着实验的进行而下降。 (3)大鼠可卡因自身给药消退阶段的建立。在该实验阶段中,采用以同等注射剂量的生理盐水替换可卡因注射的方法进行成瘾后消退,且在整个过程中保留药物相关环境刺激暗示(灯光和声音)。顺利完成训练的动物进入10天的可卡因消退期,共有20只动物完成实验并达到消退期最后连续2天打药次数不超过训练平台期平均打药次数的20%的成功标准,1小时内动物生理盐水的注射次数逐步降低并稳定在3.86±0.50,而无效鼻触次数也由初期的较高水平逐渐降低。 (4)人工合成Tat-A2对于可卡因直接引燃的觅药行为恢复没有影响。
[Abstract]:Drug addiction is to lose the ability to control continuous compulsive drug use is the main characteristic of chronic relapsing brain disease, is caused by the interaction of biological, behavioral and environmental factors. In treatment and Research on the long, difficult to overcome relapse is its appearance. At the initial stage of use will produce pleasure or relieve the pain, continue to use can lead to adaptive changes in the central nervous system; in dependence, and once the drug will produce withdrawal symptoms. The drug self administration and recovery (extinction) - (reinstatement) model is now recognized when the study of drug addiction relapse behavior model is one of the better simulation of human addiction in different stages of development, including, intravenous self-administration, drug self-administration subsided, drug self-administration direct ignition / environmental induction / recovery stage. The model induced by stress A drug delivery mode with a fixed ratio of 1 (FR1) was established, and the self medication model was established, then the self medication behavior was subsided, and finally the self medication behavior recovery test was carried out.
The purpose of this study is to establish a recovery recovery model of cocaine in rats, and discuss the modeling. Detect the effect of a synthetic LTP blocking peptide, Tat-A2, on the recovery of cocaine's direct drug igniting behavior, and discuss the results.
The main experimental results are as follows
(1) the key to the establishment of the self medication model and the key to success is external vein catheterization and maintenance. Surgical operation, intubation length, postoperative patency, infection or inflammation can all affect the duration of intubation.
(2) rats FRl cocaine self-administration of addictive behavior successfully established. After 6 days of artificial and 14 day rat self-administration training, 2 hours a day training period animal injection of cocaine (0.75mg/kg/inj.) the number gradually increased and stabilized at 33.17 + 1.45 times, and the number of invalid nose contact with the experiment was decreased.
(3) rat cocaine self-administration regression stage is established. In the experimental stage, the method of replacing cocaine injection with saline equivalent dose of addiction subsided after and during the whole process of drug related environmental stimuli that retain (light and sound). The successful completion of the training of the animal into 10 days cocaine paracmasis, a total of 20 successful standard animal experiment and finally reached complete subsidise period for 2 consecutive days of pesticide does not exceed the average number of Dayao training platform of 20%, the number of injections within 1 hours of animal physiological saline gradually reduced and stabilized at 3.86 + 0.50, and the invalid nose contact but also by the number of high level early decreased gradually.
(4) artificial synthesis of Tat-A2 has no effect on the recovery of drug foraging behavior of cocaine direct ignition.

【学位授予单位】：陕西师范大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R749.61;R-332

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