Diabetes attenuates psychological stress-elicited 5-HT secretion in the prefrontal cortex but not in the amygdala of mice
Diabetes attenuates psychological stress-elicited 5-HT secretion in the prefrontal cortex but not in the amygdala of mice
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DOI：
10.1016/j.brainres.2007.02.001
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发表时间：
2007-05-25
期刊：
影响因子：
2.9
通讯作者：
Kamei, Junzo
中科院分区：
文献类型：
--
作者：
Miyata, Shigeo;Yamada, Naoko;Kamei, Junzo
众所周知，糖尿病广泛影响中枢神经系统的功能。然而，没有体内研究评估了调节情绪的关键区域前额皮质（PFC）和杏仁核中的5-羟色胺（5-HT）释放系统。我们通过小鼠体内微透析技术研究了链脲霉素（STZ）诱导的糖尿病对PFC和杏仁核细胞外5-羟色胺水平的影响。此外，我们还研究了心理应激对5-HT分泌的影响。基础和选择性5-羟色胺再摄取抑制剂西酞普兰（1 μ M）在糖尿病小鼠PFC和杏仁核中积累的5-羟色胺水平保持不变。在糖尿病小鼠的PFC中，开放平台应激引起的升高的5- ht分泌显著减少，这种迟钝的反应通过亚慢性胰岛素预处理（5 U/kg, s.c，每日两次）得以正常化。糖尿病对pfc中KCl （100 mM）刺激的5-HT释放无显著影响。在杏仁核中，糖尿病对应激引起的5-HT分泌无影响。与非糖尿病小鼠相比，糖尿病小鼠在升高的开放平台试验中表现出更长时间的冻结。此外，胰岛素处理的糖尿病小鼠的冷冻时间明显短于糖尿病小鼠。总之，我们目前的研究结果表明，糖尿病以特定部位的方式减弱了对应激刺激的血清素能反应。此外，我们认为可能是应激引起的5-HT释放功能障碍，而不是基础5-HT释放功能障碍，导致糖尿病小鼠恐惧相关行为的表达增加。(c) 2007 Elsevier B.V.版权所有
It is well established that diabetes widely affects the functioning of the central nervous system. However, no in vivo study assessed the serotonin (5-HT)-releasing system in the prefrontal cortex (PFC) and amygdala - the crucial regions regulating emotion. We investigated the effects of streptozotocin (STZ)-induced diabetes on the levels of extracellular 5-HT in the PFC and amygdala by using an in vivo microdialysis technique in mice. In addition, the effects of psychological stress on 5-HT secretion were also examined. The basal and the selective 5-HT reuptake inhibitor citalopram (1 mu M)-accumulated 5-HT levels remained unchanged in both the PFC and amygdala of diabetic mice. The elevated open platform stress-elicited 5-HT secretion was significantly decreased in the PFC of diabetic mice, and this blunted response was normalized by sub-chronic pretreatment with insulin (5 U/kg, s.c., twice daily). Diabetes had no significant effect on the KCl (100 mM)stimulated 5-HT release in the PFC. In the amygdala, diabetes had no effect on the stress-elicited 5-HT secretion. Diabetic mice exhibited prolonged freezing as compared to the nondiabetic mice in the elevated open-platform test. In addition, insulin-treated diabetic mice showed the significant shorter duration of freezing than that in diabetic mice. In conclusion, our present findings indicate that diabetes attenuates the serotonergic response to stressful stimuli in a site-specific fashion. In addition, we suggest the possibility that the dysfunction of stress-elicited 5-HT release, but not basal 5-HT release, causes the increased expression of fear-related behavior in diabetic mice. (c) 2007 Elsevier B.V. All rights reserved.