Impact of ketamine administration on chronic unpredictable stress-induced rat model of depression during extremely low-frequency electromagnetic field exposure: Behavioral, histological and molecular study

Brain Behav. 2023 May;13(5):e2986. doi: 10.1002/brb3.2986. Epub 2023 Apr 9.

Abstract

Objectives: In the study, we examined the effects of ketamine and extremely low-frequency electromagnetic fields (ELF-EMF) on depression-like behavior, learning and memory, expression of GFAP, caspase-3, p53, BDNF, and NMDA receptor in animals subjected to chronic unpredictable stress (CUS).

Methods: After applying 21 days of chronic unpredictable stress, male rats received intraperitoneal (IP) of ketamine (5 mg/kg) and then were exposed to ELF-EMF (10-Hz, 10-mT exposure conditions) for 3 days (3 h per day) and behavioral assessments were performed 24 h after the treatments. Instantly after the last behavioral test, the brain was extracted for Nissl staining, immunohistochemistry, and real-time PCR analyses. Immunohistochemistry (IHC) was conducted to assess the effect of ketamine and ELF-EMF on the expression of astrocyte marker (glial fibrillary acidic protein, GFAP) in the CA1 area of the hippocampus and medial prefrontal cortex (mPFC). Also, real-time PCR analyses were used to investigate the impacts of the combination of ketamine and ELF-EMF on the expression of caspase3, p53, BDNF, and NMDA receptors in the hippocampus in rats submitted to the CUS procedure. Results were considered statistically significant when p < .05.

Results: Our results revealed that the combination of ketamine and ELF-EMF increased depression-like behavior, increased degenerated neurons and decreased the number of GFAP (+) cells in the CA1 area and mPFC, incremented the expression of caspase-3, and reduced the expression of BDNF in the hippocampus but showed no effect on the expression of p53 and NMDA-R.

Conclusions: These results reveal that combining ketamine and ELF-EMF has adverse effects on animals under chronic unpredictable stress (CUS).

Keywords: depression; extremely low-frequency electromagnetic field; ketamine; stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor
  • Caspase 3
  • Depression / etiology
  • Electromagnetic Fields / adverse effects
  • Ketamine* / pharmacology
  • Male
  • Rats
  • Tumor Suppressor Protein p53

Substances

  • Ketamine
  • Caspase 3
  • Brain-Derived Neurotrophic Factor
  • Tumor Suppressor Protein p53