Hypothalamic modulation of the biowarning processes caused by the emotional stress

为了阐明内源性化学物质在情绪应激引起的行为异常中的功能作用，研究了固定应激对食物摄入和下丘脑外侧区（LHA）神经活动的影响。固定2小时后观察到每日食物摄入量显著减少。注射甲塞吉特（5 mg/kg，每日1次）可拮抗固定所致厌食症3小时，而注射纳洛烷无作用。为了进一步研究5 -羟色胺神经元的活性与固定应激的关系，我们研究了自由活动大鼠LHA中5 -羟色胺能系统的活性和单个神经元的活性变化。在固定应激下，观察到5 -羟色胺代谢产物5 - HIAA细胞外浓度显著升高，下丘脑神经元活性变化随之降低。脑微透析与HPLC/ECD研究也明确了固定诱导的下丘脑血清素释放。这些结果表明，固定诱导的厌食症至少部分是通过下丘脑的血清素能机制介导的。采用体内微透析技术对脾去甲肾上腺素（NA）进行慢性监测。固定化应激导致NA释放增加到约800%的基础释放，同时抑制脾脏自然杀伤（NK）细胞活性。脾交感神经手术去神经能显著降低NA升高的水平，并抑制固定诱导的NK活性抑制作用。这些结果提示NA在脾脏的神经免疫调节中具有重要的调控作用。

To clarify the functional roles of endogenous chemical substances on the behavioral abnormalities caused by the emotional stress, the effects of immobilization stress on food intake and on neural activity in the lateral hypothalamic area(LHA)were investigated. Significant reduction of daily food intake was observed after 2 hr immobilization. Injection of methysergide(5 mg/kg, i. p.)antagonized the immobilization-induced anorexia for 3hr, while injection of naloxane had no effect. To further investigate the activity of serotonin neurons in relation to immobilization stress, the activity of the serotonergic system and single neuron activity changes in the LHA were' investigated in freely behaving rats. A significant increase in the extracellular concentration of 5, HIAA, a metabolic product of serotonin, and concomitant decrease in activity changes of the hypothalamic neurons were observed following the immobilization stress. Brain microdialysis with HPLC/ECD study also clarified the immobilization-induced serotonin release in the hypothalamus. These results suggest that immobilization-induced anorexia is mediated at least in part through serotonergic mechanisms in the hypothalamus.In vivo microdialysis technique was further used for chronic monitoring of the splenic noradrenaline(NA). Immobilization stress caused an increase in the NA release to about 800% of the basal release in conjunction with the suppression of natural killer(NK)cell activity in the spleen. Surgical denervation of the splenic sympathetic nerve significantly attenuated the increased level of NA and it also inhibited the immobilization-induced suppressive effect on the NK activity. These results suggest that NA has an important role in the control of the neuroimmunomodulation in the spleen.