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Article

Sustained antidepressant action of the N‑methyl‑D‑aspartate receptor antagonist MK‑801 in a chronic unpredictable mild stress model

  • Authors:
    • Bang‑Kun Yang
    • Jun Qin
    • Ying Nie
    • Jin‑Cao Chen
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China, Department of Neurosurgery, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442600, P.R. China, Department of Children's Medical Center, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442600, P.R. China
  • Pages: 5376-5383
    |
    Published online on: October 18, 2018
       https://doi.org/10.3892/etm.2018.6876
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Abstract

(5S,10R)‑5‑methyl‑10,11‑dihydro‑5H‑dibenzo(A,D)cyclohepten‑5,10‑imine hydrogen maleate (MK‑801) is an N‑methyl‑D‑aspartate non‑competitive antagonist that possesses useful biological properties, including anticonvulsant and anesthetic activities. Studies have indicated the rapid antidepressant effects of MK‑801 in animal models. However, there are no reports concerning a sustained antidepressant effect in the chronic unpredictable mild stress (CUMS) model. Furthermore, the antidepressant mechanism remains unclear. The aim of the present study was to examine the effects of MK‑801 (0.1 mg/kg) and rapastinel (10 mg/kg) on depression‑like behavior in CUMS mice and measure the protein expression of brain‑derived neurotrophic factor (BDNF), α‑amino‑3‑hydroxy‑5‑methyl‑4‑isoxazolepropionic acid receptor (GluA1) and phosphorylated mammalian target of rapamycin (p‑mTOR). In the tail suspension and forced swim tests, MK‑801 significantly attenuated the increased immobility time in CUMS mice compared with the vehicle group. In the sucrose preference test, a single‑dose injection of MK‑801 significantly ameliorated the decreased sucrose preference in CUMS mice compared with the vehicle group. Western blot analyses indicated that MK‑801 significantly attenuated the decreased BDNF, GluA1 and p‑mTOR protein levels in the medial prefrontal cortex (mPFC), dentate gyrus (DG) and CA3 of the hippocampi of CUMS mice. Conversely, this compound had no effect on increased BDNF, GluA1 and p‑mTOR protein levels in the nucleus accumbens of CUMS mice. Therefore, the present study revealed the sustained antidepressant effects of MK‑801 in the CUMS model. Furthermore, synaptogenesis and neuronal regeneration in the prelimbic regions of mPFC, DG and CA3 of the hippocampus may be implicated as mechanisms that promote a sustained antidepressant response.
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Copy and paste a formatted citation
Spandidos Publications style
Yang BK, Qin J, Nie Y and Chen JC: Sustained antidepressant action of the N‑methyl‑D‑aspartate receptor antagonist MK‑801 in a chronic unpredictable mild stress model. Exp Ther Med 16: 5376-5383, 2018.
APA
Yang, B., Qin, J., Nie, Y., & Chen, J. (2018). Sustained antidepressant action of the N‑methyl‑D‑aspartate receptor antagonist MK‑801 in a chronic unpredictable mild stress model. Experimental and Therapeutic Medicine, 16, 5376-5383. https://doi.org/10.3892/etm.2018.6876
MLA
Yang, B., Qin, J., Nie, Y., Chen, J."Sustained antidepressant action of the N‑methyl‑D‑aspartate receptor antagonist MK‑801 in a chronic unpredictable mild stress model". Experimental and Therapeutic Medicine 16.6 (2018): 5376-5383.
Chicago
Yang, B., Qin, J., Nie, Y., Chen, J."Sustained antidepressant action of the N‑methyl‑D‑aspartate receptor antagonist MK‑801 in a chronic unpredictable mild stress model". Experimental and Therapeutic Medicine 16, no. 6 (2018): 5376-5383. https://doi.org/10.3892/etm.2018.6876
Copy and paste a formatted citation
x
Spandidos Publications style
Yang BK, Qin J, Nie Y and Chen JC: Sustained antidepressant action of the N‑methyl‑D‑aspartate receptor antagonist MK‑801 in a chronic unpredictable mild stress model. Exp Ther Med 16: 5376-5383, 2018.
APA
Yang, B., Qin, J., Nie, Y., & Chen, J. (2018). Sustained antidepressant action of the N‑methyl‑D‑aspartate receptor antagonist MK‑801 in a chronic unpredictable mild stress model. Experimental and Therapeutic Medicine, 16, 5376-5383. https://doi.org/10.3892/etm.2018.6876
MLA
Yang, B., Qin, J., Nie, Y., Chen, J."Sustained antidepressant action of the N‑methyl‑D‑aspartate receptor antagonist MK‑801 in a chronic unpredictable mild stress model". Experimental and Therapeutic Medicine 16.6 (2018): 5376-5383.
Chicago
Yang, B., Qin, J., Nie, Y., Chen, J."Sustained antidepressant action of the N‑methyl‑D‑aspartate receptor antagonist MK‑801 in a chronic unpredictable mild stress model". Experimental and Therapeutic Medicine 16, no. 6 (2018): 5376-5383. https://doi.org/10.3892/etm.2018.6876
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