Insights into serotonergic and antioxidant mechanisms involved in antidepressant-like action of 2-phenyl-3-(phenylselanyl)benzofuran in mice

Gall, Jéssica Iara; Alves, Amália Gonçalves; Júnior, Luiz Roberto Carraro; Rech, Taís da Silva Teixeira; Neto, José S. S.; Alves, Diego; Soares, Mayara Sandrielly Pereira; Spohr, Luíza; Spanevello, Rosélia Maria; Brüning, César Augusto; Bortolatto, Cristiani F.

doi:10.1016/j.pnpbp.2020.109956

Cited by 22 publications

(26 citation statements)

References 59 publications

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“…From these results, it can be inferred that the antidepressant-like effect of SeI can involve 5-HT 2A/C receptors. Our findings corroborate previous studies, which have associated the 5-HT 2A/C receptors with the antidepressant-like activity of other organoselenium compounds in mice. − 5-HT 2 receptors are highly expressed in many regions of the brain related to humor regulation, suggesting that the mood disorders could be regulated by their activation . The 5-HT 2C subtype receptor agonists present activity in the FST, with an antidepressant-like effect in mice, and genetic ablation of 5-HT 2A receptors potentiated the depressive-like effect of chronic corticosterone administration .…”

Section: Resultssupporting

confidence: 90%

Antidepressant-Like Effect of a Selenoindolizine in Mice: In Vivo and In Silico Evidence for the Involvement of the Serotonergic 5-HT_2A/C Receptors

Garcia

Besckow

Espíndola

et al. 2022

ACS Chem. Neurosci.

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The monoaminergic dysfunction plays a central role in major depressive disorder (MDD), a mental disturbance associated with constant feeling of sadness and lack of interest. The available treatments do not present a desirable efficacy and some of them provoke several adverse effects. In this context, organoselenium compounds and molecules containing the indolizine nucleus have demonstrated interesting pharmacological properties, including antidepressant-like effects. In this study, the antidepressant-like effect of 2-phenyl-1-(phenylselanyl)indolizine (SeI), a selenium-containing indolizine derivative, was investigated on the forced swimming test (FST) and on the tail suspension test (TST) in male Swiss mice. The involvement of the serotonergic system in this effect was also accessed. The selenium compound SeI (10−100 mg/kg, intragastrical (i.g.)) was administered 0.5 h before the behavioral tests, and it diminished the immobility on both FST and TST experiments, which is an indication of antidepressant-like effect. No changing in the locomotor motion was observed in the open-field test (OFT). The anti-immobility effect of SeI was not altered by the preadministration of the selective serotonergic receptor antagonists ondansetron (1 mg/kg, intraperitoneally (i.p.), antagonist of 5-HT 3 receptor) and WAY100635 (0.1 mg/kg, subcutaneous route (s.c.), antagonist of 5-HT 1A receptor). In contrast, the preadministration of ketanserin (1 mg/kg, i.p., antagonist of 5-HT 2A/C receptor) blocked this effect, demonstrating that the antidepressant-like effect of SeI involves 5-HT 2A/C . In addition, molecular docking studies showed a strong interaction between SeI and the receptors of 5-HT 2A and 5-HT 2C . The toxicological results demonstrated that SeI has low potential to cause adverse effects in mice. It was found that the antidepressant-like effect of SeI is related to modulation of the serotonergic system, and this selenium compound could be included in new treatment approaches for MDD.

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Section: Resultssupporting

confidence: 90%

Antidepressant-Like Effect of a Selenoindolizine in Mice: In Vivo and In Silico Evidence for the Involvement of the Serotonergic 5-HT_2A/C Receptors

Garcia

Besckow

Espíndola

et al. 2022

ACS Chem. Neurosci.

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“…In protocol 2, considering that animals would receive 20 times the compound (20 days, once a time/day), our research group decided use the dose of 1 mg/kg CMI based on the previous study with organic compounds (Pesarico et al, 2016 ). Regarding the fluoxetine treatment, in the first protocol, we used 10 mg/kg of fluoxetine because previous studies demonstrated that acute administration of fluoxetine had no effect in doses lower than 10 mg/kg, whereas in protocol 2 we used 1 mg/kg because chronic administration of fluoxetine has a significant effect in the behavioral tests (Ratajczak et al, 2019 ; Gall et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

Short- and Long-Term Repeated Forced Swim Stress Induce Depressive-Like Phenotype in Mice: Effectiveness of 3-[(4-Chlorophenyl)Selanyl]-1-Methyl-1H-Indole

Pesarico

Birmann

Pinto

et al. 2020

Front. Behav. Neurosci.

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“…Based on this, structural modifications in the “SeBZF core” were performed by insertion of different electronic groups in the SeR moiety, and the most promising compound (SeBZF 3 ) was selected. Like SeBZF 1 , functionalized compounds of a SeBZF class (SeBZF 2–5 ) were previously tested and exhibited in vitro brain antioxidant capacity; however, their neuroprotective potential in vivo had not yet been investigated. Here, pioneering findings concerning the psychopharmacology of SeBZF 3 in mice were reported.…”

Section: Resultsmentioning

confidence: 99%

“…Selenium is an essential trace element eliciting important functions in the brain, which varies from antioxidant protection to neuronal signaling, and its benefits in improving mood are described . Moreover, organoselenium compounds have been widely used in the field of preclinical screening for antidepressant activity. − …”

Section: Introductionmentioning

confidence: 99%

Antidepressant Potential of a Functionalized 3-Selanyl Benzo[b]Furan Compound in Mice: Focus on the Serotonergic System

Rech

Ribeiro

Castro

et al. 2023

ACS Chem. Neurosci.

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The present study investigated the antidepressant-like potential of a functionalized 3-selanyl benzo[b]furan (SeBZF) in male Swiss mice. To evaluate possible antidepressant-like actions, the compounds SeBZF1–5 (50 mg/kg, intragastric, i.g., route) were acutely screened in the tail suspension tests (TSTs). The compound 3-((4-methoxyphenyl)selanyl)-2-phenylbenzofuran (SeBZF3) was then selected. Dose–response and time–response curves revealed that SeBFZ3 exerts antidepressant-like effects in the TST (5–50 mg/kg) and forced swimming test (FST; 50 mg/kg). Additional tests demonstrated that pretreatment with receptor antagonists WAY100635 (5-HT1A; 0.1 mg/kg, subcutaneous route), ketanserin (5-HT2A/C; 1 mg/kg, intraperitoneal, i.p.), or ondansetron (5-HT3; 1 mg/kg, i.p.) blocked the SeBZF3 antidepressant-like effects (50 mg/kg) in the TST. In addition, the coadministration of subeffective doses of SeBZF3 (1 mg/kg, i.g.) and fluoxetine (a selective serotonin reuptake inhibitor; 5 mg/kg, i.p.) produced synergistic action. A high dose of SeBZF3 (300 mg/kg) did not produce oral acute toxicity. The present results provide evidence for the antidepressant-like action of SeBZF3 and its relative safety, as well as predict the possible interactions with the serotonergic system, aiding in the development of novel options to alleviate psychiatric disabilities.

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Insights into serotonergic and antioxidant mechanisms involved in antidepressant-like action of 2-phenyl-3-(phenylselanyl)benzofuran in mice

Cited by 22 publications

References 59 publications

Antidepressant-Like Effect of a Selenoindolizine in Mice: In Vivo and In Silico Evidence for the Involvement of the Serotonergic 5-HT_2A/C Receptors

Antidepressant-Like Effect of a Selenoindolizine in Mice: In Vivo and In Silico Evidence for the Involvement of the Serotonergic 5-HT_2A/C Receptors

Short- and Long-Term Repeated Forced Swim Stress Induce Depressive-Like Phenotype in Mice: Effectiveness of 3-[(4-Chlorophenyl)Selanyl]-1-Methyl-1H-Indole

Antidepressant Potential of a Functionalized 3-Selanyl Benzo[b]Furan Compound in Mice: Focus on the Serotonergic System

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Insights into serotonergic and antioxidant mechanisms involved in antidepressant-like action of 2-phenyl-3-(phenylselanyl)benzofuran in mice

Cited by 22 publications

References 59 publications

Antidepressant-Like Effect of a Selenoindolizine in Mice: In Vivo and In Silico Evidence for the Involvement of the Serotonergic 5-HT2A/C Receptors

Antidepressant-Like Effect of a Selenoindolizine in Mice: In Vivo and In Silico Evidence for the Involvement of the Serotonergic 5-HT2A/C Receptors

Short- and Long-Term Repeated Forced Swim Stress Induce Depressive-Like Phenotype in Mice: Effectiveness of 3-[(4-Chlorophenyl)Selanyl]-1-Methyl-1H-Indole

Antidepressant Potential of a Functionalized 3-Selanyl Benzo[b]Furan Compound in Mice: Focus on the Serotonergic System

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Antidepressant-Like Effect of a Selenoindolizine in Mice: In Vivo and In Silico Evidence for the Involvement of the Serotonergic 5-HT_2A/C Receptors

Antidepressant-Like Effect of a Selenoindolizine in Mice: In Vivo and In Silico Evidence for the Involvement of the Serotonergic 5-HT_2A/C Receptors