不同时程应激对大鼠行为、免疫和交感神经系统反应的影响

研究旨在研究不同时程情绪应激诱导的大鼠行为、免疫和神经内分泌反应的动态变化及其相互关系。实验采用一种在程序性饮水的固定时间点不确定性给予大鼠空瓶刺激诱发其情绪反应的应激模式，测定不同时程（14，21和28天）应激对大鼠行为、交感神经系统反应、体液免疫功能及体重增长的影响。结果表明，情绪应激导致大鼠攻击行为显著增加，且在整个应激过程中情绪应激组大鼠的攻击行为都被稳定地诱导；不同时程的情绪应激均导致大鼠特异性抗OVA抗体水平明显降低，且降低的程度类似；在情绪应激的第14天和28天应激组大鼠血中去甲肾上腺素水平明显高于对照组，但后者升高的水平明显低于前者。此外，14天应激明显抑制大鼠的体重增长，但随着应激时程的延长，体重增长逐渐恢复。这些结果表明，随着应激时程的延长，大鼠行为、免疫和神经内分泌反应的适应性改变存在时程差异，有助于进一步了解应激诱发的各种反应间的复杂关系

The Dynamic Changes of Behavioral, Immune and Sympathetic Responses to Chronic Stress in Rats

Previous studies have shown that emotional stress induced by randomly giving an empty water bottle to rats during watering periods for 14 consecutive days activated both the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, leading to the increased blood levels of corticosterone and norepinephrine. It also elicited attacking and exploring behaviors, suppressed the level of specific anti-ovalbumin IgG antibody production which was negatively related to norepinephrine level. However, three day empty bottle presentation had no significant effect on anti-OVA antibody production. These results suggest that the duration of stressors determines the consequences of body reactions induced by stress, at least, humoral immune responses. In order to examine whether the duration of stress exerts an accumulative effect or an adaptive effect on body reactions, the present study was designed to investigate the dynamic changes in behavioral, immune and neuroendocrine responses of rats that were subjected to chronic emotional stress with different durations. Male Wistar rats were divided into four groups: (1) emotional stress (induced by randomly giving an empty water bottle to rats at set watering time)(n=19); (2) physiological stress (given neither empty water bottles nor water during the same watering periods as for emotional stress group) (n=19); (3) control 1 (allowed free access to water during watering periods)(n=15); and (4) control 2 (given water ad libitum during the whole experimental periods)(n=15). Behavioral changes, humoral immune responses and the reaction of sympathetic nervous system were measured and compared during different days(14,21 and 28 days) of stress. The behaviors observed included attacking, exploring and grooming. Norepinephrin levels in plasma were determined using high-performance liquid chromatography. Serum levels of IgG antibodies to Ovalbumin were determined by enzyme linked immunosorbent assay. It was found that emotional stress stably induced aggressive behavior of rats over the whole experimental period. Compared with controls, rats subjected to 14,21 or 28 days of stress showed decrease in the level of specific anti-OVA antibody to a similar degree. Both 14-day and 28-day stress activated the sympathetic nervous system, leading to the increased blood levels of norepinephrine. However, a decline of norepinephrine level was also obvious from 14-day to 28-day stress. The body weight showed an early decrease during the first 14-day stress period but it was gradually recovered after prolonged stress exposure. Taken together, these results demonstrated different adaptive processes of behavior, immune, neuroendocrine and physical responses to chronic stress, and may be helpful for further understanding the complex relationships among various stress responses.