Brain mechanism and conditioning of emotional behavior induced by immunological stress

点击翻译按钮获取中文摘要

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.