The impact of dexmedetomidine on ketamine-induced neurotoxicity and cognitive impairment in young mice

Background

The potential neuroprotective effects of dexmedetomidine against ketamine-induced neurotoxicity remain inconclusive. This study aims to investigate the influence of dexmedetomidine on ketamine-induced neuronal apoptosis and neurodevelopmental toxicity.

Methods

In vitro experiments employed concentrations of 0.1 uM for dexmedetomidine and 50 uM for ketamine individually as well as their combination. Changes in apoptotic proteins and dendritic development in neurons were assessed after a 6-h exposure to the drugs with evaluations conducted 24 hs' post-treatment. In vivo experiments entailed intraperitoneal administration starting from postnatal Day 7 (P7) continuously for 3 days (P7–P9) using dosages of 100 mg/kg for ketamine and 1 mg/kg for dexmedetomidine alone or combined. Learning, memory and motor coordination abilities were evaluated via rotary rod tests and shuttle box experiments at P30 and P60, respectively.

Results

Dexmedetomidine effectively mitigated ketamine-induced apoptosis in hippocampal neurons but did not alleviate associated dendritic developmental abnormalities. Although causing reduced motor coordination in mice, no improvement was observed with regard to this effect or reaction speed when treated with dexmedetomidine alongside ketamine.

Conclusion

This study demonstrates that while dexmedetomidine can mitigate ketamine-induced neuronal apoptosis, it has limited impact on its associated neurodevelopmental toxicities.