Psychopharmacology (Berl). 2025 Sep 19. doi: 10.1007/s00213-025-06906-8. Online ahead of print.
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.
PMID:40970956 | DOI:10.1007/s00213-025-06906-8
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