Dysfunction of Serotonergic and Dopaminergic Neuronal Systems in the Antidepressant-Resistant Impairment of Social Behaviors Induced by Social Defeat Stress Exposure as Juveniles.
Dysfunction of Serotonergic and Dopaminergic Neuronal Systems in the Antidepressant-Resistant Impairment of Social Behaviors Induced by Social Defeat Stress Exposure as Juveniles.
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DOI：
10.1093/ijnp/pyy038
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发表时间：
2018-09-01
期刊：
影响因子：
--
通讯作者：
Noda Y
中科院分区：
文献类型：
--
作者：
Hasegawa S;Miyake Y;Yoshimi A;Mouri A;Hida H;Yamada K;Ozaki N;Nabeshima T;Noda Y
人们对成年后暴露于社会失败压力的啮齿动物中单胺能神经元系统的作用进行了广泛的研究。在本研究中，我们研究了单胺能神经元系统在青少年社会失败压力暴露引起的社会行为损害中的作用。幼年雄性 C57BL/6J 小鼠连续 10 天暴露在社交失败压力下。从最后一次应激暴露后 1 天开始，服用地昔帕明、舍曲林和阿立哌唑 15 天。在最后一次压力暴露后 1 天和 15 天评估社会行为。测定暴露于压力的小鼠大脑特定区域的单胺周转率。青少年时期的压力暴露会导致青少年小鼠的社交行为受损。在表现出社交行为受损的小鼠中，特定大脑区域的血清素和多巴胺周转率有所下降，但去甲肾上腺素则没有下降。急性和重复给予地昔帕明、舍曲林和阿立哌唑未能减轻社会行为损害，而重复给予舍曲林和阿立哌唑的组合显示出累加的减轻作用。这些发现表明，青少年时期的社交失败压力暴露会通过血清素能和多巴胺能神经系统的功能障碍，导致青少年社交行为的治疗抵抗性损害。舍曲林和阿立哌唑的组合可作为一种新的治疗策略，用于治疗有不良青少年经历的青少年的难治性应激相关精神疾病。
Extensive studies have been performed on the role of monoaminergic neuronal systems in rodents exposed to social defeat stress as adults. In the present study, we investigated the role of monoaminergic neuronal systems in the impairment of social behaviors induced by social defeat stress exposure as juveniles. Juvenile, male C57BL/6J mice were exposed to social defeat stress for 10 consecutive days. From 1 day after the last stress exposure, desipramine, sertraline, and aripiprazole were administered for 15 days. Social behaviors were assessed at 1 and 15 days after the last stress exposure. Monoamine turnover was determined in specific regions of the brain in the mice exposed to the stress. Stress exposure as juveniles induced the impairment of social behaviors in adolescent mice. In mice that showed impairment of social behaviors, turnover of serotonin and dopamine, but not noradrenaline, was decreased in specific brain regions. Acute and repeated administration of desipramine, sertraline, and aripiprazole failed to attenuate the impairment of social behaviors, whereas repeated administration of a combination of sertraline and aripiprazole showed additive attenuating effects. These findings suggest that social defeat stress exposure as juveniles induces the treatment-resistant impairment of social behaviors in adolescents through dysfunction in the serotonergic and dopaminergic neuronal systems. The combination of sertraline and aripiprazole may be used as a new treatment strategy for treatment-resistant stress-related psychiatric disorders in adolescents with adverse juvenile experiences.
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影响因子：
4.7
作者：
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通讯作者：
Bönisch H
影响因子：
4.1
作者：
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通讯作者：
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影响因子：
168.9
作者：
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通讯作者：
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影响因子：
5.3
作者：
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通讯作者：
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影响因子：
3.6
作者：
KUDRYAVTSEVA, NN;BAKSHTANOVSKAYA, IV;KORYAKINA, LA
通讯作者：
KORYAKINA, LA