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Chronic Phencyclidine Induces Inflammatory Responses and Activates GSK3β in Mice

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Abstract

Use of phencyclidine (PCP) in rodents can mimic some aspects of schizophrenia. However, the underlying mechanism is still unclear. Growing evidence indicates that neuroinflammation plays a significant role in the pathophysiology of schizophrenia. In this study, we focused on inflammatory responses as target of PCP for inducing schizophrenia-like symptoms. 3-month-old C57BL/6J mice received daily injections of PCP (20 mg/kg, i.p.) or saline for one week. PCP-injected mice produced schizophrenia-like behaviours including impaired spatial short-term memory assessed by the Y-maze task and sensorimotor gating deficits in a prepulse inhibition task. Simultaneously, chronic PCP administration induced astrocyte and microglial activation in both the cortex and hippocampus. Additionally, the proinflammatory cytokine interleukin-1β was significantly up-regulated in PCP administrated mice. Furthermore, PCP treatment decreased ratio of the phospho-Ser9 epitope of glycogen synthase kinase-3β (GSK3β) over total GSK3β, which is indicative of increased GSK3β activity. These data demonstrate that chronic PCP in mouse produces inflammatory responses and GSK3β activation.

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Acknowledgments

This work was supported by grants from the Manitoba Health Research Council, and the Canadian Institutes of Health Research to Dr. X. M. Li, S. Zhu is a recipient of the graduate studentships from the Manitoba Health Research Council.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, MB, R3E 0T6, Canada

    Shenghua Zhu & Jun-Feng Wang

  2. Department of Clinical Psychiatry, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, People’s Republic of China

    Hongxing Wang

  3. Department of Human Anatomy and Cell Science, Faculty of Medicine, University of Manitoba, Winnipeg, MB, R3E 0J9, Canada

    Ruoyang Shi & Jiming Kong

  4. Department of Psychosomatic Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, People’s Republic of China

    Ruiguo Zhang

  5. Mental Health Center, Shantou University, Shantou, 515063, Guangdong, People’s Republic of China

    Junhui Wang

  6. Department of Psychiatry, Faculty of Medicine, University of Manitoba, Winnipeg, MB, R3E 3N4, Canada

    Lynda Kong

  7. Institute of Acumox and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, 250355, People’s Republic of China

    Yingxia Sun

  8. The First Hospital Affiliated to Henan University, Henan University, Kaifeng, 475001, Henan, People’s Republic of China

    Jue He

  9. Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, 1E7.31 Walter C. Mackenzie Health Sciences Centre, Edmonton, AB, T6G 2B7, Canada

    Xin-Min Li

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  1. Shenghua Zhu
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  10. Jun-Feng Wang
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Correspondence to Xin-Min Li.

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Zhu, S., Wang, H., Shi, R. et al. Chronic Phencyclidine Induces Inflammatory Responses and Activates GSK3β in Mice. Neurochem Res 39, 2385–2393 (2014). https://doi.org/10.1007/s11064-014-1441-9

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  • DOI: https://doi.org/10.1007/s11064-014-1441-9

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