Obesity exacerbates chemically-induced neurodegeneration. N-methyl-D-aspartate (NMDA) antagonists such as ketamine prevent excitotoxicity and are neuroprotective against acute brain injury, but can also be toxic. In low doses they induce reversible neuronal injury, but in higher doses they cause irreversible degeneration of cerebrocortical neurons. This study was designed to evaluate the neurotoxic effect of ketamine on obesity-induced neurotoxicity in the young mouse brain.

Five-week-old female wild and obese type (C57BL6) mice were randomly allocated into three groups (n=6 each) receiving a single intraperitoneal injection of (i) saline (control); (ii) ketamine (50 mg/kg); (iii) or ketamine (100 mg/kg). Three hours after ketamine administration, their brains were prepared histologically for quantitative assessment of the number of posterior cingulate/retrosplenial (PC/RS) neurons with vacuolation at a specific rostrocaudal level.

Pyramidal neurons containing cytoplasmic vacuoles in layers III and IV of the PC/RS cortex were observed in all groups of mice, except wild-type mice that received saline injections. Ketamine produced a dose-dependent vacuolization in both types of mice, which was more prominent in obese mice (P < 0.05).

Administration of ketamine in young obese mice can exacerbate neurotoxicity.