Adolescent morphine exposure induced long-term cognitive impairment and prefrontal neurostructural abnormality in adulthood in male mice

Opioids abuse in adolescence is becoming a pressing public health issue. While evidence suggests that exposure to opioids during adolescence leads to lasting alterations in brain development, the long-term cognitive implications in adulthood remain uncertain. We developed a male mouse model of adole...

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Main Authors: Ye Lu, Yijie Guo, Lulu Sun, Tong Liu, Ziqing Dong, Min Jia, Lixia Zhuo, Fangyuan Yin, Yongsheng Zhu, Xiancang Ma, Yunpeng Wang
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Heliyon
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405844024168132
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author Ye Lu
Yijie Guo
Lulu Sun
Tong Liu
Ziqing Dong
Min Jia
Lixia Zhuo
Fangyuan Yin
Yongsheng Zhu
Xiancang Ma
Yunpeng Wang
author_facet Ye Lu
Yijie Guo
Lulu Sun
Tong Liu
Ziqing Dong
Min Jia
Lixia Zhuo
Fangyuan Yin
Yongsheng Zhu
Xiancang Ma
Yunpeng Wang
author_sort Ye Lu
collection DOAJ
description Opioids abuse in adolescence is becoming a pressing public health issue. While evidence suggests that exposure to opioids during adolescence leads to lasting alterations in brain development, the long-term cognitive implications in adulthood remain uncertain. We developed a male mouse model of adolescent morphine exposure and used the 5-choice serial reaction time task (5‐CSRTT), along with the open field, novel object recognition, Y maze and Barnes maze tests, to assess changes in cognitive behavior. We found that exposure to morphine during adolescence led to deficits in multidimensional cognitive functions in mice, including attention, information processing speed, and behavior inhibition. Notable, these impairments persisted into adulthood. Furthermore, the morphine-exposed mice exhibited decreased learning efficiency and spatial memory. Adolescent morphine exposure also induced significant and persistent morphological changes and synaptic abnormalities in medial prefrontal cortex (mPFC) neurons, which may be responsible for cognitive impairments in adulthood. Together, our study suggests that opioid exposure during adolescence profoundly affects cognitive development and emphasizes that opioid-induced disruption of neurons in adolescence may link mPFC-associated cognitive impairments in adulthood.
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publisher Elsevier
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series Heliyon
spelling doaj-art-080e1bd6025b4afaa93571a779aacdb32025-08-20T01:59:38ZengElsevierHeliyon2405-84402024-12-011023e4078210.1016/j.heliyon.2024.e40782Adolescent morphine exposure induced long-term cognitive impairment and prefrontal neurostructural abnormality in adulthood in male miceYe Lu0Yijie Guo1Lulu Sun2Tong Liu3Ziqing Dong4Min Jia5Lixia Zhuo6Fangyuan Yin7Yongsheng Zhu8Xiancang Ma9Yunpeng Wang10Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China; College of Forensic Science, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, ChinaDepartment of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China; Shaanxi Key Laboratory of Biological Psychiatry, Xi'an, Shaanxi, 710061, ChinaCollege of Forensic Science, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, ChinaDepartment of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, ChinaDepartment of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, ChinaDepartment of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, ChinaDepartment of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, ChinaSchool of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, 211166, ChinaCollege of Forensic Science, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, ChinaDepartment of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China; Shaanxi Key Laboratory of Biological Psychiatry, Xi'an, Shaanxi, 710061, China; Corresponding author. Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China; Shaanxi Key Laboratory of Biological Psychiatry, Xi'an, Shaanxi, 710061, China; Lead Contact, China; Corresponding author. Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.Opioids abuse in adolescence is becoming a pressing public health issue. While evidence suggests that exposure to opioids during adolescence leads to lasting alterations in brain development, the long-term cognitive implications in adulthood remain uncertain. We developed a male mouse model of adolescent morphine exposure and used the 5-choice serial reaction time task (5‐CSRTT), along with the open field, novel object recognition, Y maze and Barnes maze tests, to assess changes in cognitive behavior. We found that exposure to morphine during adolescence led to deficits in multidimensional cognitive functions in mice, including attention, information processing speed, and behavior inhibition. Notable, these impairments persisted into adulthood. Furthermore, the morphine-exposed mice exhibited decreased learning efficiency and spatial memory. Adolescent morphine exposure also induced significant and persistent morphological changes and synaptic abnormalities in medial prefrontal cortex (mPFC) neurons, which may be responsible for cognitive impairments in adulthood. Together, our study suggests that opioid exposure during adolescence profoundly affects cognitive development and emphasizes that opioid-induced disruption of neurons in adolescence may link mPFC-associated cognitive impairments in adulthood.http://www.sciencedirect.com/science/article/pii/S2405844024168132AdolescenceMorphineCognitionMemoryMedial prefrontal cortex
spellingShingle Ye Lu
Yijie Guo
Lulu Sun
Tong Liu
Ziqing Dong
Min Jia
Lixia Zhuo
Fangyuan Yin
Yongsheng Zhu
Xiancang Ma
Yunpeng Wang
Adolescent morphine exposure induced long-term cognitive impairment and prefrontal neurostructural abnormality in adulthood in male mice
Heliyon
Adolescence
Morphine
Cognition
Memory
Medial prefrontal cortex
title Adolescent morphine exposure induced long-term cognitive impairment and prefrontal neurostructural abnormality in adulthood in male mice
title_full Adolescent morphine exposure induced long-term cognitive impairment and prefrontal neurostructural abnormality in adulthood in male mice
title_fullStr Adolescent morphine exposure induced long-term cognitive impairment and prefrontal neurostructural abnormality in adulthood in male mice
title_full_unstemmed Adolescent morphine exposure induced long-term cognitive impairment and prefrontal neurostructural abnormality in adulthood in male mice
title_short Adolescent morphine exposure induced long-term cognitive impairment and prefrontal neurostructural abnormality in adulthood in male mice
title_sort adolescent morphine exposure induced long term cognitive impairment and prefrontal neurostructural abnormality in adulthood in male mice
topic Adolescence
Morphine
Cognition
Memory
Medial prefrontal cortex
url http://www.sciencedirect.com/science/article/pii/S2405844024168132
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