Adolescent morphine exposure induced long-term cognitive impairment and prefrontal neurostructural abnormality in adulthood in male mice
Ye Lu,
Yijie Guo,
Lulu Sun,
Tong Liu,
Ziqing Dong,
Min Jia,
Lixia Zhuo,
Fangyuan Yin,
Yongsheng Zhu,
Xiancang Ma,
Yunpeng Wang
Affiliations
Ye Lu
Department 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, China
Yijie Guo
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
Lulu Sun
College of Forensic Science, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
Tong Liu
Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
Ziqing Dong
Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
Min Jia
Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
Lixia Zhuo
Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
Fangyuan Yin
School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, 211166, China
Yongsheng Zhu
College of Forensic Science, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
Xiancang Ma
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; Corresponding author. Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
Yunpeng Wang
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.
