20.500.12556/RUL-168110 Increased sensitivity to psychomotor effects of ketamine enantiomers in the Wistar-Kyoto depression model Ketamine, a fast-acting antidepressant, is a racemic mixture, composed of equal amounts of R- and S-ketamine. Preclinical studies are comparing them to better understand their role in therapeutic and undesirable effects. An important research gap is that studies do not use long clinically relevant protocols to compare the desired and undesired effects of ketamine enantiomers in modeled and control animals. In our preclinical study, we explored the behavioral effects of R- and S-ketamine at 10 mg/kg in clinically relevant treatment protocol using Wistar-Kyoto rats as a depression model and Wistar rats as a control. Undesirable psychomotor effects were evaluated with locomotor stimulation and sensitization, ataxia, and stereotypy. Persistent effects associated with therapeutic outcomes were evaluated by measuring working memory, anxiety, and behavioral despair. We found that S-ketamine has stronger acute psychomotor effects compared to R-ketamine and that Wistar-Kyoto rats are more sensitive to these effects compared to Wistar rats. After repeated treatment, sensitization to locomotor stimulating effects, and tolerance to ataxic effects of S-ketamine develops. We found no persistent changes due to ketamine treatments. Taken together, our results may indicate that depressed patients would be more prone to negative side effects of ketamine, compared to healthy controls. However, after repeated treatment, tolerance to side effects may develop and make the treatment more tolerable. Future preclinical and clinical studies are needed to address neurobiological mechanisms and clinical relevance of higher sensitivity to the psychomotor effects of ketamine, and the development of tolerance to psychomotor effects of ketamine in depressed individuals. antidepressant depression enantiomers ketamine model of depression psychomotor effects Wistar-Kyoto antidepresivi depresija enantiomeri ketamin model depresije psihomotorični učinki Wistar-Kyoto true false true Angleški jezik Slovenski jezik Članek v reviji 2025-03-28 14:07:43 2025-03-28 14:07:44 2025-03-29 04:14:36 0000-00-00 00:00:00 2025 0 0 Str. 307-317 Vol. 184 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.89 0022-3956 10.1016/j.jpsychires.2025.02.061 230490371 1-s2.0-S0022395625001402-main.pdf 1-s2.0-S0022395625001402-main.pdf 1 F3B0B6D0C9F24CBFC7A64E59FC8A43D5 95573433e69d611e8496de837ce3bcac2022ce63924386b7562b36a870c42516 c408bd02-0bd4-11f0-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=201135 https://www.sciencedirect.com/science/article/pii/S0022395625001402 0 9a6923fe-0bd4-11f0-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=201133 Medicinska fakulteta 0 0 0