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Rationale <p>1-(Phenylselanyl)-2-(<i>p</i>-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.</p> Objectives <p>Considering the important role that the glutamatergic system plays in the pathophysiology of depression, this study aimed to investigate the involvement of <i>N</i>-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.</p> Methods <p>For this purpose, <i>Swiss</i> male mice were pretreated with differents antagonists or agonists; 15–30&#xa0;min later, MeSeI was administered via the intragastric (i.g.) route. After an additional 30&#xa0;min, mouse behavior was evaluated using the FST.</p> Results <p>The antidepressant-like effects of MeSeI (50&#xa0;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&#xa0;µg/site, i.c.v. route). Co-administration of sub-effective doses of NMDA receptor antagonists (ketamine, 0.01&#xa0;mg/kg, intraperitoneal [i.p.] route and MK-801, 0.001&#xa0;mg/kg, i.p. route) with a sub-effective dose of MeSeI (0.5&#xa0;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&#xa0;mg/kg, i.p. route) or 6,7-dinitroquinoxaline-2,3(1<i>H</i>,4<i>H</i>)-dione (DNQX, 2.5&#xa0;µg/site, i.c.v. route) was not able to prevent the antidepressant-like effect of MeSeI (50&#xa0;mg/kg, i.g. route) in the FST.</p> Conclusions <p>Taken together, our data suggest that NMDA receptor signaling plays a role in the antidepressant-like effects of MeSeI in mice.</p>

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

  • 期刊论文

  • 发表日期：

    2025年9月19日

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  • 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

摘要

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.