Glutamatergic Mechanisms Underlying the Antidepressant-Like Effects of 1-(Phenylselanyl)-2-(p-tolyl)indolizine in Mice.

IF 3.3 3区医学 Q2 NEUROSCIENCES

Psychopharmacology Pub Date : 2025-09-19 DOI:10.1007/s00213-025-06906-8

Marcia Juciele da Rocha, Marcelo Heinemann Presa, Narryman Pinto Zuge, Kauane Nayara Bahr Ledebuhr, Carolina Aires de Oliveira, Eder João Lenardão, Filipe Penteado, Cristiani Folharini Bortolatto, César Augusto Brüning

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引用次数: 0

Abstract

Rationale: 1-(Phenylselanyl)-2-(p-tolyl)indolizine (MeSeI) is a selenoindolizine with antidepressant-like properties, modulating monoaminergic system in mice. The mechanisms underlying the antidepressant effects of MeSeI have not been fully elucidated.

Objectives: Considering the important role that the glutamatergic system plays in the pathophysiology of depression, this study aimed to investigate the involvement of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors signaling in the antidepressant-like effects of MeSeI in forced swimming test (FST) in mice.

Methods: For this purpose, Swiss male mice were pretreated with differents antagonists or agonists; 15-30 min later, MeSeI was administered via the intragastric (i.g.) route. After an additional 30 min, mouse behavior was evaluated using the FST.

Results: The antidepressant-like effects of MeSeI (50 mg/kg, i.g. route) in the FST were prevented by the pre-treatment with an NMDA receptor agonist (NMDA, 0.1 pmol/site, intracerebroventricular [i.c.v.] route) and a glycine-site NMDA receptor agonist (D-serine, 30 µg/site, i.c.v. route). Co-administration of sub-effective doses of NMDA receptor antagonists (ketamine, 0.01 mg/kg, intraperitoneal [i.p.] route and MK-801, 0.001 mg/kg, i.p. route) with a sub-effective dose of MeSeI (0.5 mg/kg, i.g. route) exerted a synergistic antidepressant-like effect in the FST in mice. However, the results show that the pre-treatment of mice with arcaine (1 mg/kg, i.p. route) or 6,7-dinitroquinoxaline-2,3(1H,4H)-dione (DNQX, 2.5 µg/site, i.c.v. route) was not able to prevent the antidepressant-like effect of MeSeI (50 mg/kg, i.g. route) in the FST.

Conclusions: Taken together, our data suggest that NMDA receptor signaling plays a role in the antidepressant-like effects of MeSeI in mice.

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1-（苯塞拉尼）-2-（对甲基苯基）吲哚嗪对小鼠抗抑郁样作用的谷氨酸能机制。

原理：1-(Phenylselanyl)-2-(p-tolyl)indolizine （MeSeI）是一种具有抗抑郁样特性的硒化吲哚嗪，调节小鼠单胺能系统。MeSeI抗抑郁作用的机制尚未完全阐明。目的：考虑到谷氨酸系统在抑郁症病理生理中的重要作用，本研究旨在探讨n -甲基- d -天冬氨酸（NMDA）和α-氨基-3-羟基-5-甲基-4-异氧唑丙酸（AMPA）受体信号在小鼠强迫游泳试验（FST）中MeSeI抗抑郁样作用中的作用。方法：为此，用不同的拮抗剂或激动剂预处理瑞士雄性小鼠；15 ~ 30min后，经胃灌胃给药。30分钟后，使用FST评估小鼠行为。结果：经NMDA受体激动剂（NMDA, 0.1 pmol/site，脑室灌胃）预处理后，MeSeI （50 mg/kg， ig给药）在FST中的抗抑郁样作用被阻断。]途径)和甘氨酸位点NMDA受体激动剂（d -丝氨酸，30µg/位点，体外循环途径）。同时给予亚有效剂量的NMDA受体拮抗剂（氯胺酮，0.01 mg/kg，腹腔注射）。]和MK-801 （0.001 mg/kg， ig给药）与MeSeI亚有效剂量（0.5 mg/kg， ig给药）对小鼠FST具有协同抗抑郁样作用。然而，结果表明，阿卡因（1 mg/kg，灌胃方式）或6,7-二硝基喹啉-2,3(1H,4H)-二酮（DNQX， 2.5µg/位点，灌胃方式）预处理小鼠FST不能阻止MeSeI （50 mg/kg，灌胃方式）的抗抑郁样作用。结论：综上所述，我们的数据表明NMDA受体信号在MeSeI对小鼠的抗抑郁作用中起作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Psychopharmacology 医学-精神病学

CiteScore

7.10

自引率

5.90%

发文量

257

审稿时长

2-4 weeks

期刊介绍： Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.