Protective Effects of Trolox on Ketamine-Induced Memory Impairments and Morphological Changes in the Brain

Background and Objective: Ketamine has demonstrated potential in treating various neuropsychiatric disorders at low doses. However, its memory-impairing and neurotoxic effects and abuse potential present limitations to its use. This study aimed to investigate ketamine's effects on memory functions, brain morphology and lipid peroxidation in a time- and dose-dependent manner and the protective effects of Trolox. Materials and Methods: Forty-eight male BALB/c mice were administered low and high doses of ketamine (10, 30 mg/kg/day, respectively) sub-chronically and chronically (7 and 21 days, respectively). A subgroup also received Trolox (20 mg/kg/day) for 21 days combined with high-dose ketamine. Following the drug administrations, behavioral tests were performed, including a modified elevated plus maze, a novel object recognition and a passive avoidance test. In the brain, malondialdehyde levels and morphology were examined. The results were analyzed using a one-way analysis of variance followed by a post hoc Tukey's test. Results: Chronic high-dose ketamine impaired spatial, emotional and recognition memory. Subchronic high-dose ketamine did not affect emotional and recognition memory but did impair spatial memory. Low-dose ketamine did not produce impairments. Malondialdehyde levels were elevated and morphological changes were evident in the chronic high-dose ketamine-applied group. These alterations were attenuated with Trolox. Conclusion: The memory-impairing and neurotoxic effects of ketamine are linked to increased oxidative stress. Antioxidant molecules like Trolox can be practical against the toxicity of ketamine.