Early life social isolation alters corticotropin-releasing factor responses in adult rats.
Early life social isolation alters corticotropin-releasing factor responses in adult rats.
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DOI：
10.1016/j.neuroscience.2008.10.036
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发表时间：
2009-01-23
期刊：
影响因子：
3.3
通讯作者：
Forster GL
中科院分区：
文献类型：
--
作者：
Lukkes JL;Summers CH;Scholl JL;Renner KJ;Forster GL
由早期生活社会隔离引起的压力会导致压力反应和多巴胺能活性的长期改变。促肾上腺皮质激素释放因子（CRF）是一种神经递质，介导应激反应并改变肾上腺素能活动。我们测试的假设，早期生活隔离的压力增强反应CRF在成年后，通过确定CRF输注到中缝背核（dRN）的影响，5-羟色胺（5-HT）的释放在成年大鼠的延髓核（NAc），使用体内微透析。从出生后第21天开始，将幼年雄性大鼠隔离或以3只为一组饲养3周，之后将所有大鼠再分组饲养2周。在隔离/再社会化过程中，100 ng CRF注入dRN减少5-HT释放组饲养大鼠NAc。这种治疗并没有显着影响5-HT释放隔离饲养动物的NAC。与此相反，500 ng CRF输注到dRN短暂增加5-HT释放在NAc的两组饲养和隔离的动物与隔离的动物表现出更长的肾上腺素能反应。免疫印迹和免疫荧光染色的CRF受体的dRN显示，CRF 2受体水平增加的dRN的隔离饲养的动物相比，组饲养的大鼠。两者合计，结果表明，隔离在早期的发展导致CRF受体水平和CRF介导的肾上腺素能活性的变化。这些影响可能是在分离株中观察到的对应力的敏感性增加的基础。
Stress induced by early life social isolation leads to long-lasting alterations in stress responses and serotonergic activity. Corticotropin-releasing factor (CRF) is a neurotransmitter that mediates stress responses and alters serotonergic activity. We tested the hypothesis that the stress of early life isolation enhances responses to CRF in adulthood by determining the effect of CRF infusions into the dorsal raphe nucleus (dRN) on serotonin (5-HT) release in the nucleus accumbens (NAc) of adult rats using in vivo microdialysis. Juvenile male rats were either isolated or housed in groups of 3 for a 3 week period beginning on postnatal day 21 after which, all rats were group-reared for an additional 2 weeks. Following the isolation/re-socialization procedure, infusion of 100 ng CRF into the dRN decreased 5-HT release in the NAc of group-reared rats. This treatment did not significantly affect 5-HT release in the NAc of isolation-reared animals. In contrast, infusion of 500 ng CRF into the dRN transiently increased 5-HT release in the NAc of both group-reared and isolated animals with isolated animals showing a more prolonged serotonergic response. Western blot and immunofluorescent staining for CRF receptors in the dRN showed that CRF2 receptor levels were increased in the dRN of isolation-reared animals when compared to group-reared rats. Taken together, the results suggest that isolation during the early part of development causes alterations in both CRF receptor levels and CRF-mediated serotonergic activity. These effects may underlie the increased sensitivity to stress observed in isolates.
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