Hypothalamic modulation of the biowarning processes caused by the emotional stress

为阐明内源性化学物质在情绪应激引起的行为异常中的作用，研究了束缚应激对摄食量和下丘脑外侧区（LHA）神经活动的影响。固定2小时后，观察到每日摄食量显著减少。注射麦角新碱（5 mg/kg，i.（第30页）可拮抗制动引起的食欲减退3 hr，而注射纳洛酮则无此作用。为了进一步研究与制动应激有关的5-羟色胺神经元的活性，在自由行为大鼠中研究了LHA中的5-羟色胺能系统的活性和单个神经元活性变化。一个显着增加的细胞外浓度的5，HIAA，5-羟色胺的代谢产物，和伴随的活动变化的下丘脑神经元的减少被观察到以下的制动应力。HPLC/ECD脑微透析研究也阐明了固定诱导的下丘脑5-羟色胺释放。这些结果表明，制动诱导的厌食症至少部分是通过下丘脑的去甲肾上腺素能机制介导的。固定应力导致NA释放增加到基础释放的约800%，同时抑制脾脏中的自然杀伤（NK）细胞活性。手术切除脾交感神经可显著降低NA水平的升高，并抑制制动对NK活性的抑制作用。这些结果表明，NA在控制脾脏的神经免疫调节中具有重要作用。

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.