Impact of cyclosporine upon emotional and social behavior in mice
Impact of cyclosporine upon emotional and social behavior in mice
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DOI：
10.1097/01.tp.0000263332.65519.1f
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发表时间：
2007-05-27
期刊：
影响因子：
6.2
通讯作者：
Kobayashi, Eiji
中科院分区：
文献类型：
--
作者：
Sato, Yuki;Takayanagi, Yuki;Kobayashi, Eiji
背景。环孢素会引起心理副作用，但其作用机制仍有待阐明。方法。给小鼠注射环孢素（0、10、60mg/kg腹腔注射）并检查焦虑相关和社会行为指标。还通过微透析研究了前额皮质中血清素和多巴胺的释放。结果。腹膜内给予环孢素可增加小鼠血液和脑中环孢素的浓度。较高剂量的环孢素给药会减少运动活动，增加焦虑相关行为指数，并降低社交互动指数。给药减少了前额皮质中血清素和多巴胺的释放。氯氮平注射消除了注射环孢素小鼠多巴胺释放的减少并部分恢复了社会行为指数。结论。该体内模型表明高剂量的环孢素会引起前额叶功能减退。大脑皮层由于血清素和多巴胺释放减少、焦虑相关行为增加以及社交行为紊乱而导致。氯氮平部分恢复了社会行为指数。目前的研究结果与服用环孢菌素的患者具有病理相关性。
Background. Cyclosporine induces psychological side effects but its mechanisms of action remain to be elucidated.Methods. Mice were injected with cyclosporine (0, 10, 60 mg/kg intraperitoneal) and indexes of both anxiety-related and social behaviors were examined. Release of serotonin and dopamine in the prefrontal cortex was also investigated by microdialysis.Results. Intraperitoneal administration of cyclosporine increased cyclosporine concentrations in the blood and brains in mice. Cyclosporine administration at a higher-dose reduced motor activity, increased indexes of anxiety-related behavior, and decreased an index of social interaction. The administration reduced release of serotonin and dopamine in the prefrontal cortex. Clozapine administration abolished the reduced release of dopamine and partially restored the index of social behavior in cyclosporine-injected mice.Conclusions. This in vivo model suggests that cyclosporine at a high dose induced hypo-function of the prefrontal. cortex as a result of reduced release of serotonin and dopamine, increased anxiety-related behavior, and disturbed social behavior. Clozapine partially restored an index of social behavior. The present findings are pathologically relevant in patients who take cyclosporine.