Citation

Mouri A, Ukai M, Uchida M, Hasegawa S, Taniguchi M, Ito T, Hida H, Yoshimi A, Yamada K, Kunimoto S, Ozaki N, Nabeshima T, Noda Y. Neuropharmacology 2018; 133: 23-37.

Affiliation

Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, Nagoya, Japan; Department of Neuropsychopharmacology and Hospital Pharmacy, Graduate School of Medicine, Nagoya University, Nagoya, Japan; Department of Psychiatry, Graduate School of Medicine, Nagoya University, Nagoya, Japan; Japanese Drug Organization of Appropriate Use and Research, Nagoya, Japan. Electronic address: ynoda@meijo-u.ac.jp.

Copyright

(Copyright © 2018, Elsevier Publishing)

DOI

10.1016/j.neuropharm.2018.01.016

PMID

29337227

Abstract

Adverse juvenile experiences, including physical abuse, often have negative health consequences later in life. We investigated the influence of social defeat stress exposure as juveniles on neuropsychological behaviors, and the causal role of glucocorticoids in abnormal behaviors and impairment of neurogenesis in mice exposed to the stress. The juvenile (24-day-old) and adult (70-day-old) male C57BL/6J mice were exposed to social defeat stress induced by an aggressive ICR mouse. Social defeat stress exposure as juveniles, even for 1 day, induced persistent social avoidance to the unfamiliar ICR mouse in the social interaction test, but that was not observed in mice exposed to the stress as adults. Social avoidance by the stress exposure as juveniles for 10 consecutive days was observed, when the target mouse was not only unfamiliar ICR but also another C57BL/J mouse, but not an absent or an anesthetized ICR mouse. The stress exposure did not induce anxiety- and depression-like behavior in spontaneous locomotor activity, elevated plus-maze test, marble-burying test, forced swimming test, or sucrose preference test. Serum corticosterone levels increased immediately after the stress exposure. The hippocampal neurogenesis was suppressed 1 day and 4 weeks after the stress exposure. Administration of mifepristone, a glucocorticoid receptor antagonist, prior to each stress exposure, blocked the persistent social avoidance and suppression of neurogenesis. In conclusion, social avoidance induced by social defeat stress exposure as juveniles are more persistent than that as adults. These social avoidances are associated with suppression of hippocampal neurogenesis via glucocorticoid receptors.

Copyright © 2018. Published by Elsevier Ltd.

Language: en

Keywords

Glucocorticoid; Hippocampus; Juvenile; Neurogenesis; Social behaviors; Social defeat stress