Brain mechanism and conditioning of emotional behavior induced by immunological stress

感染、肿瘤和自身免疫引起的免疫应激不仅激活免疫系统，而且激活神经和内分泌系统，导致发热和促肾上腺皮质激素分泌。与此同时，情绪反应、学习和记忆障碍以及中枢疲劳等高级大脑功能紊乱也会被诱发。本研究旨在探讨免疫应激诱导情绪行为的脑机制和调节机制。本研究的结果如下：(1)认为腹腔注射聚I：C，一种合成的双链RNA，诱导了家笼大鼠跑轮活动的下降，并产生了干扰素-a和血清素转运体在大脑皮层和下丘脑的长期表达增加，这是由干扰素-a诱导的。(2)体内脑微透析显示，大鼠内侧前额叶皮层的血清素浓度长期下降，可能是由于血清素转运体的增加。(3)向内侧前额叶皮层微量注射干扰素-a可引起血清素水平下降，而选择性血清素再摄取抑制剂氟西汀可阻断血清素水平下降，提示干扰素-α诱导的血清素水平下降是由于血清素转运体表达增强所致。(4)聚I: c诱导的疲劳和焦虑均可被5 -羟色胺1A受体激动剂减弱；(5)聚I: c诱导的疲劳可被糖精水调节，而这种调节可被5 -羟色胺1A受体激动剂消除；(6)这些发现提示聚I: c诱导的感染应激模型产生中枢性疲劳和焦虑，涉及脑干扰素和5 -羟色胺系统，这些反应可被条件化。

Immunologically stress induced by infection, tumor, and autoimmunity activates not only immune system but also neural and endocrine systems, resulting in fever and ACTH secretion. At the same time disorders in higher brain functions such as emotional responses, impairment in learning and memory, and central fatigue, are also induced. The aim of the present study was to investigate brain mechanisms and conditioning of emotional behavior induced by immunological stress. The findings of the present study are as follows; (1) that intraperitoneal injection of poly I : C, a synthetic double stranded RNA, induced a decreased in running wheel activity in the home cage in rats, and produced a long-lasting increase in expression of interferon-a and serotonin transporter, which is known to be induced by interferon-a, in the cerebral cortex and hypothalamus, (2) that in vivo brain microdialysis revealed that the rat medial prefrontal cortex showed a long-lasting decrease in serotonin concentration probably due to the increased serotonin transporters, while noradrenaline concentration increased transiently and dopamine showed no changes, (3) that microinjection of interferon-a into the medial prefrontal cortex induced a decrease in serotonin levels, which was blocked by a selective serotonin reuptake inhibitor, fluoxetine, suggesting that the interferon-α-induced reduction of serotonin was due to the enhanced expression of serotonin transporter, (4) that the poly I:C-induced fatigue and anxiety were both attenuated by serotonin 1A receptor agonist, (5) that the poly I : C-induced fatigue was conditioned by drinking saccharin water, and this conditioning was extinguished by serotonin 1A receptor agonist, and (6) that these findings suggested that the poly I : C-induced infection stress model produced central fatigue and anxiety, in which brain interferon-and serotonin system were involved, and these responses could be conditioned.