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

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).

Involvement of brain-derived neurotrophic factor signaling in the pathogenesis of stress-related brain diseases

“…It was revealed that combining treatment of ELF-EMF and ketamine increased depression-like behavior, degenerated hippocampal and cortical pyramidal neurons. Furthermore, decreased BDNF and increased caspase-3 levels were also confirmed ( Salari et al, 2023 ). The beneficial effect of (2R,6R)-hydroxynorketamine [(2R,6R)-HNK], a metabolite of ketamine, has been also demonstrated.…”

“…Remarkably, it has been suggested that combining low-frequency electromagnetic fields (ELF-EMF) and ketamine, which are recognized as effective treatment against depression-like behavior, respectively, has adverse effects ( Salari et al, 2023 ). Salari et al (2023) performed behavioral, histological and molecular study using male rats received ketamine treatment and/or ELF-EMF following 3 weeks chronic unpredictable stress. It was revealed that combining treatment of ELF-EMF and ketamine increased depression-like behavior, degenerated hippocampal and cortical pyramidal neurons.…”