Antidepressant-like effect of a selenopropargylic benzamide in mice: involvement of the serotonergic system

Besckow, Evelyn Mianes; Nonemacher, Natália Tavares; Garcia, Cleisson Schossler; Espíndola, Carlos Natã da Silva; Balbom, Éverton Berwanger; Gritzenco, Fabiane; Savegnago, Lucielli; Godoi, Benhur; Bortolatto, Cristiani F.; Brüning, César Augusto

doi:10.1007/s00213-020-05600-1

Cited by 16 publications

(19 citation statements)

References 53 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: Resultsmentioning

confidence: 99%

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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

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: Resultsmentioning

confidence: 99%

“…This time was set so that the OFT was performed almost at the same time (26 min) after the pre-administration of SeI compared to the other tests (FST and TST). The 30 min pretreatment with SeI was based on previous studies with organoselenium compounds. ,− …”

Section: Methodsmentioning

confidence: 99%

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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“…Several studies suggest that the antidepressant-like action of selenium-based compounds can be mediated by serotonergic modulation. ,, SSRIs are most widely prescribed in the previous years to treat patients with depression and anxiety and exert their therapeutic action by regulating 5-HT levels and facilitating their neurotransmission . Thus, experiments were designed to investigate the contribution of different 5-HT receptors in the antidepressant-like action of SeBZF 3 in the TST, and their results can be seen in Figure .…”

Section: Resultsmentioning

confidence: 99%

“…43 In our study, the 5-HT 3 antagonist ondansetron hampered the anti-immobility effects of SeBZF3 in the TST, suggesting its involvement in its antidepressant-like properties. Interestingly, Besckow et al 25 suggested the effects of another organoselenium on 5-HT 3 receptors. However, this receptor has not been suggested to be implicated in the antidepressant-like action of SeBZF1.…”

Section: Involvement Of 5-ht 1a 5-ht 2a/2c and 5-htmentioning

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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“…Sel exerts neuroprotective effects by homeostasis regulations through several mechanisms such as alleviation of oxidative stress (Cosín-Tomàs 2019), in ammatory pathways regulation (Ataizi et al 2019) decrease in DNA destruction (Kryukov et al 2003), increasing telomere length and activity (Cao et al 2017), and modulation of numerous neurotransmitter (Yan et al 2019). Moreover, Sel intricates in the physiopathology of various psychiatric illnesses (Nogueira et al 2011) by modulating serotonergic systems (Besckow et al 2020).…”

Section: Introductionmentioning

confidence: 99%

D-galactose induced dysfunction in mice hippocampus and the possible antioxidant and neuromodulatory effects of selenium

Samad

Hafeez

Imran

2021

Environ Sci Pollut Res

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Aging is an ultimate reality that everyone has to face. D-galactose (D-gal) has been used extensively to develop aging model. Trace elements such as selenium (Sel) have been used as a potential antioxidant for neuro-protection. The present work aims to develop therapeutic agents such as Sel for the treatment of aging-induced neurological ailments such as anxiety, depression, and memory impairment. For this purpose, mice were treated with D-gal at a dose of 300 mg/ml/kg and various doses of Sel (0.175 and 0.35mg/ml/kg) for 28 days. Behavioural tests were monitored after treatment days. After the behavioural assessment mice were decapitated and their brains were collected. Hippocampi were removed from the brain for biochemical and neurochemical analysis. The present ndings of behavioural analysis showed that D-gal induced anxiety and depression-like symptoms were inhibited by both doses of Sel. D-gal induced memory alteration was also prevented by repeated doses (0.175 and 0.35mg/ml/kg) of Sel.Biochemical analysis showed that D-gal induced increase of oxidative stress marker and decrease of antioxidant enzymes in the hippocampus was prevented by Sel administration. An increase in the activity of acetylcholinesterase was also diminished by Sel. The neurochemical assessment showed that D-gal induced increased serotonin metabolism and decreased acetylcholine levels in the hippocampus were restored by repeated treatment of Sel. It is concluded that D-gal induced dysfunction in mice hippocampus caused anxiety, depression, memory impairment, oxidative stress that were mitigated by Sel via its antioxidant potential and modulating capability of serotonergic and cholinergic functions.

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Antidepressant-like effect of a selenopropargylic benzamide in mice: involvement of the serotonergic system

Cited by 16 publications

References 53 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

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

D-galactose induced dysfunction in mice hippocampus and the possible antioxidant and neuromodulatory effects of selenium

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Antidepressant-like effect of a selenopropargylic benzamide in mice: involvement of the serotonergic system

Cited by 16 publications

References 53 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

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

D-galactose induced dysfunction in mice hippocampus and the possible antioxidant and neuromodulatory effects of selenium

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Product

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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