PMID- 38097092 OWN - NLM STAT- MEDLINE DCOM- 20240108 LR - 20240108 IS - 1095-953X (Electronic) IS - 0969-9961 (Linking) VI - 190 DP - 2024 Jan TI - Multiple integrated social stress induces depressive-like behavioral and neural adaptations in female C57BL/6J mice. PG - 106374 LID - S0969-9961(23)00390-X [pii] LID - 10.1016/j.nbd.2023.106374 [doi] AB - Despite women representing most of those affected by major depression, preclinical studies have focused almost exclusively on male subjects, partially due to a lack of ideal animal paradigms. As the persistent need regarding the sex balance of neuroscience research and female-specific pathology of mental disorders surges, the establishment of natural etiology-based and systematically validated animal paradigms for depression with female subjects becomes an urgent scientific problem. This study aims to establish, characterize, and validate a "Multiple Integrated Social Stress (MISS)" model of depression in female C57BL/6J mice by manipulating and integrating daily social stressors that females are experiencing. Female C57BL/6J mice randomly experienced social competition failure in tube test, modified vicarious social defeat stress, unescapable overcrowding stress followed by social isolation on each day, for ten consecutive days. Compared with their controls, female MISS mice exhibited a relatively decreased preference for social interaction and sucrose, along with increased immobility in the tail suspension test, which could last for at least one month. These MISS mice also exhibited increased levels of blood serum corticosterone, interleukin-6 L and 1beta. In the pharmacological experiment, MISS-induced dysfunctions in social interaction, sucrose preference, and tail suspension tests were amended by systematically administrating a single dose of sub-anesthetic ketamine, a rapid-onset antidepressant. Compared with controls, MISS females exhibited decreased c-Fos activation in their anterior cingulate cortex, prefrontal cortex, nucleus accumbens and some other depression-related brain regions. Furthermore, 24 h after the last exposure to the paradigm, MISS mice demonstrated a decreased center zone time in the open field test and decreased open arm time in the elevated plus-maze test, indicating anxiety-like behavioral phenotypes. Interestingly, MISS mice developed an excessive nesting ability, suggesting a likely behavioral phenotype of obsessive-compulsive disorder. These data showed that the MISS paradigm was sufficient to generate pathological profiles in female mice to mimic core symptoms, serum biochemistry and neural adaptations of depression in clinical patients. The present study offers a multiple integrated natural etiology-based animal model tool for studying female stress susceptibility. CI - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Zhai, Xiaojing AU - Zhai X AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. FAU - Ai, Lin AU - Ai L AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. FAU - Chen, Dandan AU - Chen D AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. FAU - Zhou, Dongyu AU - Zhou D AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. FAU - Han, Yi AU - Han Y AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. FAU - Ji, Ran AU - Ji R AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. FAU - Hu, Mengfan AU - Hu M AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. FAU - Wang, Qing AU - Wang Q AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. FAU - Zhang, Moruo AU - Zhang M AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. FAU - Wang, Yuxin AU - Wang Y AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. FAU - Zhang, Chunyan AU - Zhang C AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. FAU - Yang, Jun-Xia AU - Yang JX AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. FAU - Hu, Ankang AU - Hu A AD - Laboratory Animal Center of Xuzhou Medical University, Xuzhou Medical University, Xuzhou 221004, PR China. FAU - Liu, He AU - Liu H AD - Department of Anesthesiology & Clinical Research Center for Anesthesia and Perioperative Medicine, Huzhou Central Hospital, Huzhou 313003, China; The Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou 313003, China; The Fifth School of Clinical Medicine, Zhejiang Chinese Medical University, Huzhou 313003, China; The Affiliated Central Hospital, Huzhou University, Huzhou 313003, China. Electronic address: lh121061@163.com. FAU - Cao, Jun-Li AU - Cao JL AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Department of Anesthesiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. Electronic address: caojl0310@aliyun.com. FAU - Zhang, Hongxing AU - Zhang H AD - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. Electronic address: hongxing.zhang@xzhmu.edu.cn. LA - eng PT - Journal Article DEP - 20231213 PL - United States TA - Neurobiol Dis JT - Neurobiology of disease JID - 9500169 RN - 0 (Antidepressive Agents) RN - 57-50-1 (Sucrose) SB - IM MH - Humans MH - Male MH - Female MH - Animals MH - Mice MH - Mice, Inbred C57BL MH - *Depressive Disorder MH - Antidepressive Agents MH - Brain MH - Sucrose/therapeutic use MH - Stress, Psychological/complications MH - Depression/etiology MH - Disease Models, Animal OTO - NOTNLM OT - Animal model OT - Female mice OT - Major depressive disorder OT - Overcrowding OT - Social competition OT - Social isolation OT - Social stress OT - Vicarious social defeat stress COIS- Declaration of Competing Interest None. EDAT- 2023/12/15 00:43 MHDA- 2024/01/08 06:42 CRDT- 2023/12/14 19:27 PHST- 2023/10/09 00:00 [received] PHST- 2023/11/25 00:00 [revised] PHST- 2023/12/07 00:00 [accepted] PHST- 2024/01/08 06:42 [medline] PHST- 2023/12/15 00:43 [pubmed] PHST- 2023/12/14 19:27 [entrez] AID - S0969-9961(23)00390-X [pii] AID - 10.1016/j.nbd.2023.106374 [doi] PST - ppublish SO - Neurobiol Dis. 2024 Jan;190:106374. doi: 10.1016/j.nbd.2023.106374. Epub 2023 Dec 13.