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首页> 外文期刊>The international journal of neuropsychopharmacology >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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Dysfunction of Serotonergic and Dopaminergic Neuronal Systems in the Antidepressant-Resistant Impairment of Social Behaviors Induced by Social Defeat Stress Exposure as Juveniles

机译：少年暴露于社交挫败应激所致的社交行为的抗抑郁抵抗抵抗中，血清素能和多巴胺能神经元功能障碍。

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Background 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. Methods 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. Results 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. Conclusions 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. social defeat stress , juvenile , adolescent , social behaviors , monoaminergic neuronal system Significance Statement Monoaminergic neuronal systems have attracted the attention of researchers with regard to the impairment of social behaviors induced by social defeat stress exposure as adults. However, the importance of monoaminergic neuronal systems in the impairment of social behaviors induced by exposure to social defeat stress as juveniles remains poorly understood; thus, 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. Exposure to social defeat stress as juveniles leads to the treatment-resistant impairment of social behaviors in adolescents, because of dysfunction of the serotonergic and dopaminergic neuronal systems. Repeated administration of a combination of sertraline and aripiprazole showed additive effects in attenuating this impairment of social behaviors. This may be useful as a new treatment strategy for treatment-resistant stress-related psychiatric disorders in adolescents with adverse juvenile experiences.
机译：背景技术关于成年后遭受社交挫败压力的啮齿动物中单胺能神经元系统的作用已进行了广泛的研究。在本研究中，我们调查了单胺能神经元系统在青少年遭受社会挫败压力暴露引起的社会行为受损中的作用。方法雄性C57BL / 6J雄性小鼠连续10天遭受社交挫败压力。从最后一次应激暴露后1天开始，给予地昔帕明，舍曲林和阿立哌唑15天。在最后一次压力暴露后第1和15天评估社交行为。在暴露于应激的小鼠中，大脑的特定区域确定了单胺转换。结果少年时期的应激暴露会导致青春期小鼠社交行为的损害。在表现出社交行为受损的小鼠中，特定大脑区域的5-羟色胺和多巴胺（而非去甲肾上腺素）的转换减少。急性和反复服用地昔帕明，舍曲林和阿立哌唑不能减轻对社会行为的损害，而反复服用舍曲林和阿立哌唑的组合则表现出加性衰减作用。结论这些发现表明，青少年由于缺乏血清素能和多巴胺能神经元系统的功能障碍而导致社交挫败压力暴露，导致青少年对社交行为的抗治疗性损害。舍曲林和阿立哌唑的组合可作为治疗不良少年的抗应激相关精神病的新治疗策略。社会挫败压力，少年，青少年，社会行为，单胺能神经元系统的重要意义单胺能神经元系统已引起研究人员的关注，因为成年人暴露于社会挫败压力会导致社会行为的损害。然而，单胺能神经元系统在青少年遭受社会挫败压力引起的社会行为受损中的重要性仍知之甚少;因此，在本研究中，我们调查了单胺能神经元系统在青少年遭受社会挫败压力暴露引起的社会行为受损中的作用。由于血清素能和多巴胺能神经元系统功能障碍，青少年遭受社交挫败压力会导致青少年社交行为的抗治疗性损害。重复给予舍曲林和阿立哌唑的组合显示出减轻这种社会行为损害的累加作用。这可能是治疗青少年不良经历的青少年抵抗压力相关的精神疾病的一种新的治疗策略。

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