Brain Research Lab, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
PLoS One. 2024 Mar 1;19(3):e0299379. doi: 10.1371/journal.pone.0299379. eCollection 2024.
Ketamine has gained significant attention as a fast-acting antidepressant. However, ketamine is also associated with undesirable side effects. In our preclinical study, we explored the behavioral effects of ketamine enantiomers at subanesthetic doses. During repeated intermittent treatment, we examined locomotor stimulation and sensitization, ataxia, and expression of natural behaviors (grooming and rearing). Male Wistar rats were subcutaneously treated repeatedly with either 5 mg/kg of R-ketamine or S-ketamine, 15 mg/kg of R-ketamine, S-ketamine or racemic ketamine, 30 mg/kg of racemic ketamine or saline every third day for three weeks (seven treatments overall). After the first treatment, only 15 mg/kg of S-ketamine induced locomotor stimulation, and both 15 mg/kg of S-ketamine and 30 mg/kg of racemic ketamine induced ataxia. Upon repeated administration, doses of 15 mg/kg of R-ketamine, S-ketamine, and racemic ketamine, as well as 30 mg/kg of racemic ketamine, stimulated locomotion. 15 mg/kg of R-ketamine, S-ketamine, and racemic ketamine additionally resulted in locomotor sensitization. The last administration of 15 mg/kg of S-ketamine, 15 mg/kg of racemic ketamine, and 30 mg/kg of racemic ketamine resulted in ataxia. In the case of 15 mg/kg of S-ketamine, ataxic effects were significantly weaker in comparison to the effects from the first administration, indicating tolerance. Natural behaviors were attenuated after 5 and 15 mg/kg of S-ketamine and 15 and 30 mg/kg of racemic ketamine. Neither of the R-ketamine doses produced such an effect. We conclude that S-ketamine has a stronger behavioral effect than R-ketamine.
氯胺酮作为一种快速起效的抗抑郁药引起了广泛关注。然而，氯胺酮也伴随着不良的副作用。在我们的临床前研究中，我们探索了氯胺酮对映异构体在亚麻醉剂量下的行为效应。在重复间歇性治疗中，我们检查了运动刺激和敏化、共济失调以及自然行为（梳理和饲养）的表达。雄性 Wistar 大鼠皮下重复接受 5mg/kg 的 R-氯胺酮或 S-氯胺酮、15mg/kg 的 R-氯胺酮、S-氯胺酮或外消旋氯胺酮、30mg/kg 的外消旋氯胺酮或生理盐水，每三天一次，共七次治疗。第一次治疗后，只有 15mg/kg 的 S-氯胺酮诱导运动刺激，15mg/kg 的 S-氯胺酮和 30mg/kg 的外消旋氯胺酮诱导共济失调。在重复给药后，15mg/kg 的 R-氯胺酮、S-氯胺酮和外消旋氯胺酮以及 30mg/kg 的外消旋氯胺酮刺激运动。15mg/kg 的 R-氯胺酮、S-氯胺酮和外消旋氯胺酮还导致运动敏化。最后一次给予 15mg/kg 的 S-氯胺酮、15mg/kg 的外消旋氯胺酮和 30mg/kg 的外消旋氯胺酮导致共济失调。对于 15mg/kg 的 S-氯胺酮，与第一次给药相比，共济失调的影响明显减弱，表明存在耐受性。在给予 5mg/kg 和 15mg/kg 的 S-氯胺酮以及 15mg/kg 和 30mg/kg 的外消旋氯胺酮后，自然行为均减弱。两种剂量的 R-氯胺酮均未产生这种效果。我们得出结论，S-氯胺酮的行为效应强于 R-氯胺酮。
