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Psychopharmacology

, Volume 236, Issue 7, pp 2223–2232 | Cite as

Chronic phencyclidine treatment impairs spatial working memory in rhesus monkeys

  • Bo Zhang
  • Fei Xiong
  • Yuanye Ma
  • Bing Li
  • Yu Mao
  • Zhu Zhou
  • Hualin Yu
  • JingHui Li
  • Chuanyu Li
  • Juan Fu
  • Jianhong WangEmail author
  • Xudong ZhaoEmail author
Original Investigation
  • 132 Downloads

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.

Keywords

Schizophrenia Phencyclidine Nonhuman primates Cognitive deficits Spatial delayed response 

Notes

Funding information

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).

Compliance with ethical standards

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Supplementary material

213_2019_5214_MOESM1_ESM.docx (331 kb)
ESM 1 (DOCX 330 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Yunnan Key Laboratory of Primate Biomedicine Research, Institute of Primate Translational MedicineKunming University of Science and TechnologyKunmingPeople’s Republic of China
  2. 2.Kunming Primate Research Center, Kunming Institute of ZoologyChinese Academy of SciencesKunmingPeople’s Republic of China
  3. 3.Affiliated Renhe Hospital of China Three Gorges UniversityYichangPeople’s Republic of China
  4. 4.Institute of Biophysics, Chinese Academy of SciencesBeijingPeople’s Republic of China
  5. 5.MOE Key Lab for Neuroinformation, the Clinical Hospital of Chengdu Brain Science InstituteUniversity of Electronic Science and Technology of ChinaChengduChina
  6. 6.First Affiliated Hospital of Kunming Medical UniversityKunmingPeople’s Republic of China
  7. 7.College of Biological and Environmental EngineeringBinzhou UniversityBinzhouPeople’s Republic of China

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