Dysfunction of serotonergic and dopaminergic neuronal systems in the antidepressant-resistant impairment of social behaviors induced by social defeat stress exposure as juveniles

Sho Hasegawa, Yuriko Miyake, Akira Yoshimi, Akihiro Mouri, Hirotake Hida, Kiyofumi Yamada, Norio Ozaki, Toshitaka Nabeshima, Yukihiro Noda

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Abstract

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 stressrelated psychiatric disorders in adolescents with adverse juvenile experiences.

Original languageEnglish
Pages (from-to)837-846
Number of pages10
JournalInternational Journal of Neuropsychopharmacology
Volume21
Issue number9
DOIs
Publication statusPublished - 01-01-2018

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Social Behavior
Antidepressive Agents
Sertraline
Desipramine
Brain
Inbred C57BL Mouse
Psychiatry
Rodentia
Dopamine
Serotonin
Norepinephrine
Therapeutics
Aripiprazole

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

@article{88b74c2fb70f44d087d32184f18b1138,
title = "Dysfunction of serotonergic and dopaminergic neuronal systems in the antidepressant-resistant impairment of social behaviors induced by social defeat stress exposure as juveniles",
abstract = "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 stressrelated psychiatric disorders in adolescents with adverse juvenile experiences.",
author = "Sho Hasegawa and Yuriko Miyake and Akira Yoshimi and Akihiro Mouri and Hirotake Hida and Kiyofumi Yamada and Norio Ozaki and Toshitaka Nabeshima and Yukihiro Noda",
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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. / Hasegawa, Sho; Miyake, Yuriko; Yoshimi, Akira; Mouri, Akihiro; Hida, Hirotake; Yamada, Kiyofumi; Ozaki, Norio; Nabeshima, Toshitaka; Noda, Yukihiro.

In: International Journal of Neuropsychopharmacology, Vol. 21, No. 9, 01.01.2018, p. 837-846.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Dysfunction of serotonergic and dopaminergic neuronal systems in the antidepressant-resistant impairment of social behaviors induced by social defeat stress exposure as juveniles

AU - Hasegawa, Sho

AU - Miyake, Yuriko

AU - Yoshimi, Akira

AU - Mouri, Akihiro

AU - Hida, Hirotake

AU - Yamada, Kiyofumi

AU - Ozaki, Norio

AU - Nabeshima, Toshitaka

AU - Noda, Yukihiro

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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 stressrelated psychiatric disorders in adolescents with adverse juvenile experiences.

AB - 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 stressrelated psychiatric disorders in adolescents with adverse juvenile experiences.

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DO - 10.1093/ijnp/pyy038

M3 - Article

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SP - 837

EP - 846

JO - International Journal of Neuropsychopharmacology

JF - International Journal of Neuropsychopharmacology

SN - 1461-1457

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