Comparação entre o efeito da administração aguda de R,S-cetamina e S-cetamina em camundongos expostos a estresse inescapável

Abstract

Currently, mental disorders have become increasingly evident in society, resulting in a growing search for more effective treatments. In this context, ketamine, a drug traditionally used as an anesthetic, has been gaining prominence due to its rapid action as an antidepressant drug, and is also used in cases of treatment-resistant depression. Ketamine is a racemic mixture, existing in the forms of R-ketamine, S-ketamine and R,S-ketamine. The present study analyzed the responses of the compounds R,S-ketamine and S-ketamine, both administered at a dose of 10 mg/kg after acute stress, in mice. Thus, active avoidance, tail suspension test and open field were performed to evaluate, respectively, cognition, the response related to depressive behavior, locomotion, and anxiety. The results indicated that, in the active avoidance test, both forms of ketamine did not present significant differences in relation to the control group, suggesting that ketamine does not alter cognition. In the tail suspension test, it was observed that the both R,S-ketamine and S-ketamine treated groups exhibited a shorter immobility time compared to the control group, indicating the efficacy of both forms of the drug as antidepressants. In the open field test, no changes in locomotion were observed four hours after ketamine administration. Furthermore, in the evaluation of the time spent in the center of the apparatus, it was found that the R,S-ketamine treated group, but not S-ketamine, remained longer in the center compared to the control group, indicating a possible anxiolytic effect of this isomer. Therefore, the data from this study demonstrate that both forms of ketamine at the dose used did not affect the aversive memory of the animals, as well as being effective in reducing the behavioral response related to depression. However, only R,S-ketamine exhibited an anxiolytic potential. Furthermore, the animals' locomotion was not affected by either form of the drug. More studies are needed to investigate the effects of these isomers at different doses and at different periods of administration, in order to obtain more findings about the ketamine potential against mental disorders.