Long-lasting anti-despair and anti-anhedonia effects of (S)-norketamine in social isolation-reared mice

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY Journal of pharmacological sciences Pub Date : 2023-12-14 DOI:10.1016/j.jphs.2023.12.005

Rei Yokoyama , Momoko Higuchi , Wataru Tanabe , Shinji Tsukada , Hisato Igarashi , Kaoru Seiriki , Takanobu Nakazawa , Atsushi Kasai , Yukio Ago , Hitoshi Hashimoto

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Abstract

Alternatives to ketamine without psychotomimetic properties for the treatment of depression have attracted much attention. Here, we examined the anti-despair and anti-anhedonia effects of the ketamine metabolites (S)-norketamine ((S)-NK), (R)-NK, (2S,6S)-hydroxynorketamine, and (2R,6R)-hydroxynorketamine in a mouse model of depression induced by social isolation. All ketamine metabolites examined had acute (30 min after administration) anti-despair-like effects in the forced swim test, but only (S)-NK showed a long-lasting (1 week) effect. Additionally, only (S)-NK improved reduced motivation both 30 min and 24 h after injection in the female encounter test. These results suggest that (S)-NK has potent and long-lasting antidepressant-like effects.

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(S)-诺基他敏对社会隔离饲养小鼠的长效抗绝望和抗失神作用

氯胺酮的替代品--不具有拟精神药物特性的氯胺酮治疗抑郁症引起了广泛关注。在这里，我们研究了氯胺酮代谢物(S)-norketamine（(S)-NK）、(R)-NK、(2S,6S)-hydroxynorketamine和(2R,6R)-hydroxynorketamine在社会隔离诱导的抑郁症小鼠模型中的抗绝望和抗失神作用。在强迫游泳试验中，所有氯胺酮代谢物都具有急性（给药后30分钟）抗绝望样效应，但只有(S)-NK显示出持久（1周）的效应。此外，在雌性相遇试验中，只有（S）-NK 能在注射后 30 分钟和 24 小时内改善降低的动机。这些结果表明，(S)-NK 具有强效和持久的抗抑郁样作用。

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来源期刊

Journal of pharmacological sciences 医学-药学

CiteScore

6.20

自引率

2.90%

发文量

104

审稿时长

31 days

期刊介绍： Journal of Pharmacological Sciences (JPS) is an international open access journal intended for the advancement of pharmacological sciences in the world. The Journal welcomes submissions in all fields of experimental and clinical pharmacology, including neuroscience, and biochemical, cellular, and molecular pharmacology for publication as Reviews, Full Papers or Short Communications. Short Communications are short research article intended to provide novel and exciting pharmacological findings. Manuscripts concerning descriptive case reports, pharmacokinetic and pharmacodynamic studies without pharmacological mechanism and dose-response determinations are not acceptable and will be rejected without peer review. The ethnopharmacological studies are also out of the scope of this journal. Furthermore, JPS does not publish work on the actions of biological extracts unknown chemical composition.