Brain Research Laboratory, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška cesta 4, 1000, Ljubljana, Slovenia. Electronic address: anamarija.banjac@mf.uni-lj.si.
2 papers in the library · 9 citations · publishing 2024-2025
Ketamine's antidepressant potential is limited by side effects such as motor impairment. In rats, repeated low doses of ketamine enantiomers produced distinct behavioral changes. S-ketamine at 15 mg/kg caused initial locomotor stimulation and ataxia, while repeated administration led to locomotor sensitization and tolerance to ataxia. R-ketamine at 15 mg/kg also stimulated locomotion and caused sensitization but did not induce ataxia or reduce natural behaviors like grooming and rearing. Higher doses of racemic ketamine (30 mg/kg) produced both stimulation and ataxia. Overall, S-ketamine had stronger behavioral effects than R-ketamine, suggesting R-ketamine may have a more favorable side-effect profile.
Ketamine, a fast-acting antidepressant, is a racemic mixture of R- and S-ketamine. In a preclinical study using Wistar-Kyoto rats (a depression model) and Wistar rats (controls), researchers compared behavioral effects of R- and S-ketamine at 10 mg/kg in a clinically relevant treatment protocol. S-ketamine produced stronger acute psychomotor effects (locomotor stimulation, ataxia, stereotypy) than R-ketamine, and Wistar-Kyoto rats were more sensitive to these effects. After repeated treatment, sensitization to locomotor stimulation and tolerance to ataxic effects of S-ketamine developed. No persistent changes in working memory, anxiety, or behavioral despair were found. Results suggest depressed individuals may be more prone to negative side effects, but tolerance may develop with repeated treatment.