Increased sensitivity to psychomotor effects of ketamine enantiomers in the Wistar-Kyoto depression model

Elersič, Kristian (avtor), Banjac, Anamarija (avtor), Živin, Marko (avtor), Zorović, Maja (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: antidepressant, depression, enantiomers, ketamine, model of depression, psychomotor effects, Wistar-Kyoto
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2025
• Št. strani: Str. 307-317
• Številčenje: Vol. 184
• PID: 20.500.12556/RUL-168110
• UDK: 616.89
• ISSN pri članku: 0022-3956
• DOI: 10.1016/j.jpsychires.2025.02.061
• COBISS.SI-ID: 230490371
• Datum objave v RUL: 28.03.2025

Gradivo je del revije

• Naslov: Journal of psychiatric research
• Založnik: Elsevier
• ISSN: 0022-3956
• COBISS.SI-ID: 5639434

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: antidepresivi, depresija, enantiomeri, ketamin, model depresije, psihomotorični učinki, Wistar-Kyoto

Projekti

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: P3-0171
• Naslov: Plastičnost živčevja v fizioloških in patofizioloških razmerah

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Program financ.: Young researchers