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mTOR Expression in Hippocampus and Prefrontal Cortex Is Downregulated in a Rat Model of Schizophrenia Induced by Chronic Administration of Ketamine

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Abstract

Schizophrenia is a severe chronic neuropsychiatric disorder, and it negatively affects individuals’ quality of life, but the pathogenesis of schizophrenia remains unclear. This study aimed to explore whether the administration of ketamine in rats causes changes in mTOR (mechanistic/mammalian target of rapamycin) expression in the hippocampus and prefrontal cortex. Ketamine was used to establish an animal model of schizophrenia. Rats were randomly divided into four groups: control group (normal saline), low-dose group (15 mg/kg ketamine), middle-dose group (30 mg/kg ketamine), and high-dose group (60 mg/kg ketamine). The rats were intraperitoneally injected with ketamine or normal saline twice a day (9 AM and 9 PM) for 7 consecutive days. Immunohistochemistry was used to detect mTOR protein expression in the hippocampus and prefrontal cortex from rats at 13 h after the last treatment. Using immunohistochemistry, the expression of the mTOR protein was localized exclusively in the CA3 region of the hippocampus and in the Cg1 region of the prefrontal cortexes. Ketamine at 60 mg/kg decreased the expression of mTOR protein in the brain of rats. Ketamine successfully established a rat model of schizophrenia. This study helps elucidate the mechanisms of ketamine-induced schizophrenia and provides novel insights for drug discovery and development.

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Funding

This study was supported by the National Natural Sciences Foundation of China [Grant No. 81373239], the Yunnan Applied Basic Research/Kunming Medical University Union Project [Grant Nos. 2017FE467-(166) and 2018FE001-(011)], and the Kunming Medical University Innovation Group Project [Grant Nos. CXTD201604 and CXTD201803].

Author information

R-F Xie and L-C Liao: study concept and design, analysis and interpretation of data, drafting of the manuscript, and obtained funding. R-F Xie and J-M Xie contributed equally to this work. R-F Xie, J-M Xie, Y Ye, X-Y Wang: the acquisition of samples or data, statistical analysis, review of the manuscript, and obtained funding. F Chen, L Yang, Y-Y Yan: statistical analysis, review of the manuscript, and material supports.

Correspondence to Linchuan Liao.

Ethics declarations

All animal experiments were performed according to the Guide for the Care and Use of Laboratory Animals 8th Edition. The study was approved by the Ethics Committee of Kunming Medical University (Kunming, China).

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

All authors declare that the submitted manuscript does not contain previously published data, and it is also not being under consideration for publication elsewhere.

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Runfang Xie and Jiming Xie are joint first authors.

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Xie, R., Xie, J., Ye, Y. et al. mTOR Expression in Hippocampus and Prefrontal Cortex Is Downregulated in a Rat Model of Schizophrenia Induced by Chronic Administration of Ketamine. J Mol Neurosci 70, 269–275 (2020). https://doi.org/10.1007/s12031-019-01476-9

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Keywords

  • Ketamine
  • mTOR
  • Hippocampus
  • Prefrontal cortex
  • Schizophrenia
  • Expression