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大鼠强迫性 奖赏寻求行为新模型及行为标志物初步筛选作者
Alternative TitleA novel compulsive reward-seeking behavior model in rats and preliminary screening of behavioral markers
张宁
Contributor白云静
2021-06
Abstract目的:1)本研究采用自主研发的全自动行为箱,探索啮齿类动物在面对不可逃避的电击惩罚时对高价值奖赏(性奖赏)的寻求行为,建立以不断重复、不计代价为主要特征的强迫性奖赏寻求行为模型,并比较了正常群体(盐水处理)和成瘾药物(吗啡)暴露群体的强迫性奖赏寻求行为。2)采用本模型考察强迫倾向的个体差异,揭示正常群体和药物暴露群体中出现强迫样行为的比例,同时考察强迫性奖赏寻求行为的行为学特征。3)本研究还初步考察三种特质因素(焦虑、奖赏敏感性及新颖反应性)在药物(吗啡)暴露后的改变,及其与强迫性奖赏寻求行为的预测关系。 方法:本研究共93只成年雄性Sprague Dawley (SD)大鼠,通过交配筛选后接受了高架十字迷宫、糖精水偏好和新颖反应性三种测试(前测) ),被 随机分成两组,吗啡组接受连续 5天的大剂量吗啡腹腔注射, 对照 组 接受 连续 5天生理盐水注射 。 停止注射 (戒断 第 6 7天分别 再次 接受高架十字迷 宫 和糖精水偏好测试(后测),同时适应 全自动 行为箱 2天。从戒断第 8天开始,全部动物 在 行为 箱中 进行连续 16天的奖赏寻求行为测试 ,每天 1次(共 16 sessions 。 每次测试包括 1个自由趋近测试和 14个受限趋近测试,后者由 7个伴有电击 、 电击信号灯的惩罚试次( Punishment P)和 7个 不伴有电击、电击信号灯的 非惩罚试次Non-Punishment NP)组成,两 种测试 随机出现。测量并记录以下行为指标:触发试次数、完成试次数、完成试次比例,在行为箱内各区域( zone1、 2、 3)停留时间,首次到达 zone2、 3的潜伏期。 以最后四次测试(Session 13-16)中P试次里平均zone3停留时间来衡量动物的强迫性程度。 结果:1)吗啡暴露致奖赏寻求行为改变:基线阶段(Session 1-3),吗啡动物在靠近奖赏区域(zone3)停留时间更短。引入电击惩罚的阶段(Session 4-16),吗啡动物触发和完成试次数均显著低于盐水动物,但试次完成率更高;吗啡动物zone3停留时间显著高于、而zone1停留时间显著低于盐水动物;吗啡动物首次到达zone3的潜伏期显著低于盐水动物;2)以最后四次测试中P试次里平均zone3停留时间来衡量动物的强迫性程度(明知有电击惩罚的情况下仍然忍受电击接近性奖赏的程度),通过聚类分析,将全部动物区分为具有不同行为表型的亚群组:强迫型,中间型和非强迫型,各表型群组的各奖赏寻求行为指标差异显著;在控制药物处理、测试(session)和试次类别协变量的情况下,发现完成试次数、完成试次比例和zone3停留时间与动物强迫性水平正相关,zone1、zone2停留时间和首次到达zone3潜伏期与强迫性水平负相关;3)38只盐水动物中的2只(频率5%),55只吗啡动物中的10只(频率14%),被鉴定为强迫表型;与盐水动物(概率5%,贝叶斯修正概率)相比,吗啡动物发展出强迫表型的概率更大(15%,贝叶斯修正概率); 4)强迫性水平与焦虑前测水平边缘显著相关;不同强迫性表型动物间前测焦虑、奖赏敏感性和新颖反应性没有差异,后测焦虑、奖赏敏感性也没有差异;动物强迫性水平与焦虑、奖赏敏感性和新颖寻求前测水平不相关,与焦虑、奖赏敏感性后测水平不相关。 结论:1)采用自主研制的全自动行为箱建立起啮齿类动物的强迫性奖赏寻求行为模型,根据大鼠的强迫性程度区分出具有不同强迫表型的个体;2)正常群体中少数个体具有强迫倾向,而阿片药物暴露和戒断促进部分个体的强迫样行为发生,增加强迫表型的比例;3)暂不支持焦虑、奖赏敏感性和新颖反应性与动物强迫性水平有关,或不同强迫表型亚群之间的差异。
Other AbstractObjectives: 1) In this study, we used a self-made automatic behavior box to explore rodents' seeking behavior of high-value reward (sexual reward) in face of unavoidable foot shock punishment, established a new compulsive reward-seeking behavior model characterized by constantly repetition and regardless of negative consequences, and compared reward-seeking behavior between normal group and drug (morphine) exposure group. 2) We use this model to investigate the individual differences of compulsive level, to evaluate the proportion of rats obsessive-like behaviors in the normal and drug-exposure groups, and to investigate behavioral features of compulsive reward-seeking behaviors. 3) In this study, three behavioral markers (anxiety, reward sensitivity, and novelty seeking) and their changes after drug (morphine) treatment were preliminarily investigated to see if they can predict reward-seeking behavior of rats in the model. Methods: In this study, a total of 93 adult male Sprague Dawley rats(SD) satisfied the mating screening criterion and underwent three tests (pretest) :the elevated cross maze test, saccharin preference test and novel reactivity test. The morphine group received Binge-like morphine treatment for 5 successive days, while the saline group received only saline injections for five days. On the 6th and 7th day after withdrawal, the elevated cross maze test and saccharine preference test were re-tested, and the behavior box was adapted at the same time. All animals were tested for reward-seeking behavior for 16 consecutive days in the automated behavior box from 8th day since withdrawal, 1 session per day. Each session includes 1 free approach test and 14 restricted approach tests which consists of 7 Punishment trials(P) accompanied by shock and shock light and 7 non-punishment trials (NP) without shock and shock light and the two kinds of trials appeared randomly. The following behavioral indexes were measured and recorded: number of triggered trials, number of completed trials, percentage of completed trials; time spent in zone1, time spent in zone2 and time spent in zone 3; lantency to first entries in zone2 and lantency to first entries in zone3. The compulsion level of animal was measured by the average time spent in zone3 in the last four sessions (Session13-16) in P trials. Results: 1) The reward-seeking behavior of morphine and saline animals was different: the morphine animals stayed longer in zone2 and shorter in zone3 during baseline period (Session1-3). In Session4-16, the number of trials triggered and completed by morphine animals was significantly lower than that of saline animals, but the percentage of completed trials of morphine animals was higher. Morphine animals were more likely to enter zone3 in which rats might received foot shock. Time spent in zone3 of morphine animals was significantly higher than that of saline animals, while the time spent in zone1 of morphine animals was significantly lowerthan of saline animals. The lantency to first entries in zone3 for morphine animals was significantly lower than that for saline animals. 2) Average time spent in zone3 during last four sessions in P trials was selected as an index reflecting animal’s compulsivity level and the extent to which animals staying in zone3, keeping close to female ras and tolerating electric foot-shock even though they knew there was negative punishment in zone3. According to this index, we distinguished groups of animals with different compulsion phenotypes: Compulsive, Intermediate and Non-Compulsive, and there are stable behavioral differences among 3 compulsion phenotype groups; under the control of pretreatment, session and trial category(P or NP), the partial correlation analysis between this index and other behavioral indexes were performed, and showes that the number of trigger trials, the percentage of trigger trials and time spent in zone3 were positively correlated with the compulsion level, while time spent in Zone1, time spent in zone2 and the the latency to first entries in zone3 were negatively correlated with the level of compulsion. 3) 2 of the 38 saline animals (frequency:5%) and 10 of the 55 morphine animals (frequency:14%) showed compulsive phenotype; Compared with 5%(adjusted probability) in saline animals, morphine animals were more likely to develop compulsive phenotype (adjusted probability:15%). 4) Compulsive level of animals was marginal significantly correlated with anxiety pretest level. There were no differences in pre-test anxiety, reward sensitivity and novel reactivity level among animals with different compulsive phenotypes, and there were no differences in post-test anxiety and reward sensitivity level among animals with different compulsive phenotypes. Compulsive level of animals was not related to anxiety, reward sensitivity and novelty seeking pre-test level, nor related to anxiety and reward sensitivity post-test level. Conclusion: 1) Compulsive reward-seeking behavior model was established in the self-made automatic box. According to the model, we distinguished 3 subgroups of animals with different compulsion phenotypes; 2) A few saline rats show compulsive tendencies, opioid exposure and withdrawal promotes the occurrence of obsessive-like behaviors in some individuals and increases the proportion of obsessive-compulsive phenotypes; 3) Anxiety, reward sensitivity and novelty-seeking were not associated with the level of compulsion, and no differences between different subgroups of compulsive phenotypes was found.
Keyword强迫性 强迫表型 阿片类物质依赖 个体差异 行为标志物
Subtype硕士
Language中文
Degree Name理学硕士
Degree Discipline应用心理
Degree Grantor中国科学院心理研究所
Place of Conferral中国科学院心理研究所
Document Type学位论文
Identifierhttp://ir.psych.ac.cn/handle/311026/39592
Collection健康与遗传心理学研究室
Recommended Citation
GB/T 7714
张宁. 大鼠强迫性 奖赏寻求行为新模型及行为标志物初步筛选作者[D]. 中国科学院心理研究所. 中国科学院心理研究所,2021.
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