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Chronic phencyclidine treatment impairs spatial working memory in rhesus monkeys

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A Correction to this article was published on 15 May 2019

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Abstract

Rationale

Phencyclidine (PCP) could induce schizophrenia (Sz) like behavior in both humans and animals, therefore, has been widely utilized to establish Sz animal models. It induced cognitive deficits, the core symptom of Sz, mainly through influencing frontal dopaminergic function. Nonhuman primate (NHP) studies demonstrated impaired object retrieval detour (ORD) and spatial delayed response (SDR) task performance by acute or chronic PCP treatment. However, NHP investigations, continually monitoring SDR performance before, during and after PCP treatment, are lacking.

Objectives

Present study investigated the long-term influence of chronic PCP treatment on SDR performance and the possible increase of SDR deficit severity and duration by the incremental dosing procedure in rhesus monkeys.

Methods

SDR task was performed repeatedly up to eight weeks after constant dosing procedure (i.m., 0.3 mg/kg, day 12-25), during which drug effects on locomotor activity and blood cortisol concentration were assessed. Incremental dosing procedure (starting dose 0.3 mg/kg, day 6-19) began five months later.

Results

Constant dosing procedure induced differential level of hyperactivity across testing days, without significant influence on blood cortisol concentration. It reduced SDR performance, until occurrence of the first and worst impairment on day 15 and 23 respectively. The impaired performance recovered to pretreatment level over one week after drug cessation. In contrast, incremental dosing procedure impaired SDR performance on the first treatment day, which recovered within treatment period.

Conclusion

Results suggested increase of SDR deficit severity by repeated PCP administrations, whereas the incremental dosing procedure did not increase SDR deficit severity and duration.

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Change history

  • 15 May 2019

    After publication of this paper, the authors determined an error in Fig. 2C.

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Funding

The authors acknowledge the support from National Science Foundation of China (NSFC 31771194, 31730039), Ministry of Science and Technology of China grant (2015CB351701, 2015CB856400), National Key Research and Development Program of China (2017YFC1001902, 2018YFC1313803), Yunnan Basic Research Program (2015FA004, 2017FA042, 2018FB114) the Strategic Priority Research Program of Chinese Academy of Science (XDB32010300) and the Natural Science Foundation of Shandong Province (ZR2015CL025).

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Author notes

  1. Bo Zhang and Fei Xiong contributed equally to this work.

Authors and Affiliations

  1. Yunnan Key Laboratory of Primate Biomedicine Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, Yunnan, People’s Republic of China

    Bo Zhang, Yuanye Ma & Chuanyu Li

  2. Kunming Primate Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, Yunnan, People’s Republic of China

    Fei Xiong, Bing Li, Yu Mao & Jianhong Wang

  3. Affiliated Renhe Hospital of China Three Gorges University, Yichang, 443000, Hubei, People’s Republic of China

    Fei Xiong

  4. Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China

    Yuanye Ma & Xudong Zhao

  5. MOE Key Lab for Neuroinformation, the Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China, Chengdu, Sichuan, China

    Yuanye Ma

  6. First Affiliated Hospital of Kunming Medical University, Kunming, 650223, Yunnan, People’s Republic of China

    Zhu Zhou, Hualin Yu & JingHui Li

  7. College of Biological and Environmental Engineering, Binzhou University, Binzhou, 256600, Shandong, People’s Republic of China

    Juan Fu

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  1. Bo Zhang
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Zhang, B., Xiong, F., Ma, Y. et al. Chronic phencyclidine treatment impairs spatial working memory in rhesus monkeys. Psychopharmacology 236, 2223–2232 (2019). https://doi.org/10.1007/s00213-019-05214-2

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