2. Academic Validation
  3. Chronic intranasal oxytocin alleviates cognitive impairment and reverses oxytocin signaling upregulation in MK801-induced mice

Chronic intranasal oxytocin alleviates cognitive impairment and reverses oxytocin signaling upregulation in MK801-induced mice

  • Psychoneuroendocrinology. 2024 Oct:168:107138. doi: 10.1016/j.psyneuen.2024.107138.
Shan Ding 1,  Yong Liu 1,  Huai Tao 2,  Yuxu Zhao 1,  Hongtao Zeng 1,  Yiding Han 1,  Shichen Wang 1,  Zhiheng Chen 3,  Yamei Tang 4,  Wenbin Guo 1
Affiliations

Affiliations

  • 1 Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China.
  • 2 Department of Biochemistry and Molecular Biology, Hunan University of Chinese Medicine, Changsha, China.
  • 3 Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China.
  • 4 Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China. Electronic address: yameitang3287@csu.edu.cn.
PMID: 39068687 DOI: 10.1016/j.psyneuen.2024.107138
Abstract

Objective: Cognitive impairment, especially impaired social cognition, is largely responsible for the deterioration of the social life of patients with schizophrenia (SZ). Oxytocin (OT) is a neuropeptide that offers promising therapy for SZ. This study aimed to explore whether OT could affect dizocilpine (MK801)-induced cognitive impairment and to investigate the effect of exogenous OT on the endogenous OT system in the hippocampus.

Methods: The SZ mouse model was established by repeated administration of dizocilpine [MK801, 0.6 mg/kg, intraperitoneal (i.p.)], and then OT (6-60 μg/kg, intranasal) or risperidone (0.3 mg/kg, i.p.) was administered to explore the effect of OT on cognitive impairment.

Results: OT at a dose of 6 μg/kg alleviated MK801-induced hyperactivity, sociability impairment, and spatial memory impairment. OT at a dose of 20 or 60 μg/kg attenuated the hyperactivity and social novelty impairment. In MK801-injected mice, the compensatory upregulation of OT mRNA in the hippocampus was reversed by three OT doses, whereas 60 μg/kg OT reversed the compensatory upregulation of CD38 protein expression.

Conclusion: OT alleviated cognitive impairment in the SZ mouse model to varying degrees, reversing the compensatory upregulation of OT signaling in the hippocampus.

Keywords

CD38; Cognitive impairment; Hippocampus; Oxytocin; Schizophrenia.

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