强迫游泳大鼠不同行为反应性的精神病理学意义研究

发布时间：2018-06-01 00:16

本文选题：强迫游泳试验 + 旷场试验　；参考：《汕头大学》2007年硕士论文

【摘要】： 背景和目的：先前的动物应激研究，主要根据应激的强度和时间来分析应激对个体的不同影响。但是，仅仅从应激的强度和时间进行应激研究，极有可能忽视了个体在不同应激环境中的主动适应行为的意义和影响。本试验在建立强迫游泳应激动物模型的基础上，观察应激大鼠的主动性行为和被动性行为变化；分析在强迫游泳实验中大鼠不同的行为反应对探索性行为、内分泌、海马结构体积及代谢物水平的影响，阐明个体在应激环境中主动性行为和被动性行为的精神病理学意义及其神经发生机制。材料和方法：选择成年雄性SD大鼠24只，体重180—200g，将大鼠随机分为2组，对照组(6只)和试验组(18只)，试验组由单次应激组(6只)、2周应激组(6只)、4周应激组(6只)组成。采用FST作为应激源，记录大鼠在应激过程中攀爬、游泳和静止的时间和次数，并根据应激过程中行为差异再次分组，将大鼠划分为主动性行为组和被动性行为组。采用OFT评测大鼠的自主行为，应激开始前和结束后分别测量一次。运用磁共振在体测量双侧海马体积和海马区N-乙酰天冬氨酸相对水平，ELISA法测定血清中皮质酮的浓度，采HPLC法离体测定海马代谢物NAA和Cr浓度以及计算NAA／Cr比值。实验结果用EXCEL2003和SPSS13.0统计软件进行分析处理。结果以均数±标准误((?)±SE)表示，采用方差分析(ANOVA)、t检验(T-test)进行组间均数比较，析因分析比较应激强度与行为适应性之间的交互作用以及各自的独立效应，Pearson法分析FST和OFT中行为学指标之间的相关性。P＜0.05为差异显著。结果：(1)应激后OFT各行为学指标与末次FST中各行为学指标相关性：游泳时间与各指标的相关性，游泳时间与穿行格数和修饰次数的相关系数r分别为0.472和0.531，有统计学意义，P＜0.05；游泳时间与竖立次数和垂直运动相关性分别为0.625和0.637，呈高度相关，P＜0.01；攀爬时间与各指标的相关性，攀爬时间与穿行格数、修饰次数、竖立次数的相关系数r分别为0.194、0.454和0.399，均无统计学意义；攀爬时间与垂直运动的相关系数r=0.469，有统计学意义，P＜0.05；静止时间与各指标的相关性，静止时间与穿行格数的相关系数r=－0.477，P＜0.05；与竖立次数、修饰次数和垂直运动的相关系数r分别为－0.672，－0.654和－0.792，显著相关，P＜0.01。中央格停留时间与以上各指标相关系数r分别为－0.139、－0.158和0.154，均无统计学意义。 (2)根据在最后一次应激任务中大鼠主动性行为和被动性行为的持续时间，对试验组大鼠进行再分组：主动性行为组和被动性行为组。主动性行为入组标准：在末次游泳应激中主动运动时间≥30s，或次数≥10次(共8只)；被动性行为入组标准：末次游泳应激中主动运动时间＜30s，，或次数＜10次(共10只)。 (3)应激后主动性行为组的中央格停留时间(3.0±0.6)和被动性行为组(4.9±2.0)高于对照组(2.4±0.4)，但各组间比较均未见统计学差异，P=0.447；对照组穿行格数(47.5±12.1)明显多与被动性行为组(15.4±4.4)，P=0.003，与主动性行为组(27.4±4.2)比较未见统计学差异，主动性行为组与被动性行为组之间比较无差别；主动性行为组的竖立次数(5.9±1.8)多于被动性行为组(2.1±0.7)和对照组(3.2±0.3)，但是无统计学差异；对照组的运动量(50.7±12.3)显著高于被动性行为组(17.5±4.9)，P=0.004，主动性行为组(33.3±5.2)与对照组和被动性行为组比较均无统计学差异；被动性行为组(5.6±0.9)的垂直运动明显低于主动性行为组(12.3±3.4)，P=0.007，两者和对照组(10.2±0.8)比较均无差异；被动性行为组的修饰次数(3.5±0.6)少于于对照组(7.0±0.7)，P=0.01，主动性行为组(6.4±1.9)与对照组和被动性行为组比较均无差异；排便数主动性行为组(1.5±0.6)、被动性行为组(2.9±0.7)和对照组(1.7±0.6)，组间比较无统计学差异(P=0.260)。 (4)应激后被动性行为组(846.393±58.094 ng／ml)血清皮质酮浓度显著高于主动性行为组(508.843±12.010 ng／ml)和对照组(191.599±47.526 ng／ml)，P分别为0.007和0.000；主动性行为组高于对照组，P=0.022。 (5)海马绝对体积比较：对照组左侧海马体积(69.552±1.705)与主动性行为组(68.912±2.264)和被动性行为组(64.241±2.247)比较无统计学差异(P=0.186)；对照组(71.905±1.541)和主动性行为组(70.062±2.129)右侧海马体积显著大于被动性行为组(63.702±1.629)，P分别为0.006和0.017。相对体积比较：主动性行为组大鼠左侧海马相对体积(0.075±0.006)大于被动性行为组(0.065±0.008)，P为0.006；对照组(0.072±0.005)和主动性行为组(0.077±0.007)右侧海马相对体积大于被动性行为组(0.064±0.006)，P分别为0.024和0.000，对照组与主动性行为组双侧比较结果均无统计学差异。 (6)应激后对照组双侧海马NAA相对水平(左侧：1.304±0.088；右侧：1.268±0.070)显著高于被动性行为组(左侧：1.107±0.103；右侧：1.119±0.133)，P分别为0.004和0.021；主动性行为组双侧(左侧：1.200±0.132：右侧：1.224±0.117)与两组比较均无统计学差异。 (7)应激后对照组(7.143±0.366)左侧海马NAA绝对浓度高于被动性行为组(5.874±0.451)，P=0.044，主动性行为组(6.419±0.310)与两者比较无统计学差异；NAA／Cr比值方面，对照组(1.323±0.094)高于被动性行为组(1.110±0.160)，P=0.015，主动性行为组(1.222±0.154)与两者比较无统计学差异。 (8)应激强度和行为反应的交互作用分析结果：中央格停留时间、穿行格数、竖立次数、修饰次数、排便粒数、垂直运动、运动量、双侧海马体积、双侧海马区代谢物水平、血清皮质酮浓度以及海马代谢物水平离体测定结果均未发现交互作用。结论：(1)在强迫游泳试验中应激大鼠的主动性行为与旷场试验中穿行格数、竖立次数和修饰行为均呈现正相关。应激大鼠的被动性行为则与旷场试验中穿行格数、竖立次数和修饰行为存在负相关。 (2)行为反应性可作为评定强迫游泳应激大鼠，是适应环境，还是适应失败的理想行为学指标。 (3)与主动性行为的应激大鼠相比，采用被动性行为的应激大鼠的自主探索活动减少，主要应激激素水平明显升高，海马体积缩小，代谢物水平下降。 (4)析因分析显示应激强度和行为反应性不存在交互作用，说明行为反应性是独立发挥作用的。
[Abstract]:Background and purpose: the previous study of animal stress is mainly based on the intensity and time of stress to analyze the different effects of stress on individuals. However, the study of stress only from the intensity and time of stress may ignore the significance and influence of the individual's active adaptation in different stressful environments. On the basis of swimming stress animal models, the active behavior and passive behavior changes in stress rats were observed, and the effects of different behavioral responses on exploratory behavior, endocrine, hippocampal volume and metabolites in forced swimming test were analyzed, and the individual active behavior and passive behavior in the stressful environment were clarified. The pathological significance of the deity and its neurogenesis.
Materials and methods: 24 adult male SD rats, weighing 180 - 200g, were randomly divided into 2 groups, the control group (6) and the test group (18 rats). The test group was composed of single stress group (6), 2 week stress group (6) and 4 week stress group (6). The time and the time of climbing, swimming and resting in stress process were recorded with FST as stress source. The rats were divided into active behavior group and passive sex group according to the difference of behavior difference during the stress process. The independent behavior of rats was measured by OFT, and the stress was measured before and after the stress. The relative level of N- acetyl aspartic acid in the bilateral hippocampal volume and the sea horse area was measured by magnetic resonance (MRI), and the ELISA method was measured. The concentration of corticosterone in the serum was determined, the concentration of NAA and Cr in the hippocampus and the ratio of NAA / Cr were measured in vitro by HPLC method. The results were analyzed with EXCEL2003 and SPSS13.0 software. The results were represented by the mean + standard error ((?) + SE), and the comparison of variance analysis (ANOVA) and t test (T-test) was used to analyze the factorial analysis ratio. The interaction between stress intensity and behavioral adaptation and their respective independent effects, Pearson analysis of the correlation between FST and OFT behavior indicators.P < 0.05 was significant.
Results: (1) the correlation between the behavioral indexes of OFT and the behavioral indexes in the last FST after stress: the correlation of swimming time with each index, the correlation coefficient r of swimming time and wear number and modification number, respectively, was 0.472 and 0.531, respectively, P < 0.05; the correlation between swimming time and vertical and vertical movement was 0.62, respectively. 5 and 0.637 were highly correlated, P < 0.01; the correlation between climbing time and each index, climbing time and crossing number, the number of modification times and the correlation coefficient r of erect times were 0.194,0.454 and 0.399, respectively. The correlation coefficient of climbing time and vertical movement was r= 0.469, P < 0.05; static time and each finger. The correlation coefficient of the standard, the correlation coefficient of the rest time and the number of crossing rows is r= 0.477, P < 0.05; the correlation coefficient r of the vertical number and the vertical motion is 0.672, 0.654 and 0.792, respectively. The relationship between the residence time of the P < 0.01. and the above indexes is 0.139, 0.158 and 0.154, respectively. Learning meaning.
(2) according to the duration of the active and passive behavior of the rats in the last stress task, the rats in the experimental group were redivided into the active behavior group and the passive sexual behavior group. The active sexual behavior group standard: the active exercise time was more than 30s in the last swimming stress, or the number of times more than 10 times (a total of 8); the passive sexual behavior entered the group. Criteria: active swimming time was less than 30s in the last swimming stress, or less than 10 times (a total of 10).
(3) the central lattice stay time (3 + 0.6) and passive sexual behavior group (4.9 + 2) were higher than those of the control group (2.4 + 0.4) after stress, but there was no statistical difference between the groups, P=0.447, and the number of walking lattices (47.5 + 12.1) in the control group was significantly more than the passive sex group (15.4 + 4.4), P=0.003, compared with the active behavior group (27.4 + 4.2). There was no difference between the active behavior group and the passive sex group, the vertical number of active behavior group (5.9 + 1.8) was more than that of the passive sex group (2.1 + 0.7) and the control group (3.2 + 0.3), but there was no statistical difference. The exercise volume of the control group (50.7 + 12.3) was significantly higher than that of the passive sex group (17.5 + 4.9), P=0.004, initiative. The sexual behavior group (33.3 + 5.2) had no statistical difference compared with the control group and the passive sex group; the vertical movement of the passive sex group (5.6 + 0.9) was significantly lower than the active behavior group (12.3 + 3.4), P=0.007, and the control group (10.2 + 0.8), and the number of modifications (3.5 + 0.6) in the passive behavior group was less than that of the control group (7 + 0.7). There was no difference between the active behavior group (6.4 + 1.9) and the control group and the passive sex group (6.4 + 1.9), the active behavior group (1.5 + 0.6), the passive sex group (2.9 + 0.7) and the control group (1.7 + 0.6). There was no statistical difference between the groups (P=0.260).
(4) the concentration of serum corticosterone in the passive behavior group (846.393 + 58.094 ng / ml) after stress was significantly higher than that in the active behavior group (508.843 + 12.010 ng / ml) and the control group (191.599 + 47.526 ng / ml), P was 0.007 and 0, respectively, and the active sex group was higher than the control group, P= 0.022..
(5) the comparison of the absolute volume of the hippocampus: the volume of the left hippocampus in the control group (69.552 + 1.705) was not significantly different from the active behavior group (68.912 + 2.264) and the passive sex group (64.241 + 2.247). The volume of the right hippocampus in the control group (71.905 + 1.541) and the active sex group (70.062 + 2.129) was significantly greater than that of the passive behavior group (63.702 + 1.705) (63.702 + 1.705). 629), P is 0.006 and 0.017., respectively.
Relative volume: the relative volume of the left hippocampus in the active behavior group (0.075 + 0.006) was greater than that of the passive behavior group (0.065 + 0.008), and P was 0.006. The relative volume of the right hippocampus in the control group (0.072 + 0.005) and the active behavior group (0.077 + 0.007) was greater than that of the passive behavior group (0.064 + 0.006), and the P was 0.024 and 0, the control group and the initiative. There was no significant difference in sexual behavior between the two groups.
(6) the relative level of bilateral hippocampal NAA in the control group (left: 1.304 + 0.088, right: 1.268 + 0.070) was significantly higher than that in passive behavior group (left: 1.107 + 0.103; right: 1.119 + 0.133), and P in 0.004 and 0.021, respectively, and there was no statistics in the active sexual group. Learning differences.
(7) the absolute concentration of NAA in the left hippocampus of the control group (7.143 + 0.366) was higher than that of the passive behavior group (5.874 + 0.451), P=0.044, the active behavior group (6.419 + 0.310) and the two groups had no statistical difference. The NAA / Cr ratio, the control group (1.323 + 0.094) was higher than the passive sex group (1.110 + 0.160), P=0.015, active sexual behavior group (1.222 + 0.154). There is no statistical difference compared with the two.
(8) the analysis of interaction between stress intensity and behavioral response: Central lattice residence time, number of crossing lines, vertical times, times of modification, number of defecation particles, vertical movement, exercise, bilateral hippocampal volume, level of metabolites in bilateral hippocampal region, serum corticosterone concentration and the results of hippocampal metabolite level in vitro determination results have not been found to be interactive.
Conclusions: (1) in the forced swimming test, the active behavior of stress rats has a positive correlation with the number of rows in the open field test, the number of erection and the modification behavior. The passive behavior of stress rats is negatively related to the number of rows in the open field test, the number of erection and the behavior of the modification.
(2) behavioral responsiveness can be used as an ideal behavioral indicator for evaluating rats with forced swimming stress.
(3) compared with the active behavior stress rats, the autonomic exploration activity of the stress rats with passive behavior decreased, the level of the main stress hormones increased significantly, the volume of the hippocampus reduced and the metabolite level decreased.
(4) factorial analysis shows that there is no interaction between stress intensity and behavioral responsiveness, indicating that behavioral responsiveness plays an independent role.
【学位授予单位】：汕头大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：D919.3

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