Insights into serotonergic and antioxidant mechanisms involved in antidepressant-like action of 2-phenyl-3-(phenylselanyl)benzofuran in mice
| Autor: | Mayara Sandrielly Pereira Soares, Cristiani F. Bortolatto, Jéssica Iara Gall, Diego Alves, Roselia Maria Spanevello, José S. S. Neto, Luiz Roberto Carraro Júnior, Luiza Spohr, Taís da Silva Teixeira Rech, César Augusto Brüning, Amália Gonçalves Alves |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
Antioxidant Ketanserin medicine.drug_class Pyridines medicine.medical_treatment Serotonin reuptake inhibitor Pharmacology Motor Activity medicine.disease_cause Serotonergic Antioxidants Piperazines 03 medical and health sciences Mice 0302 clinical medicine Serotonin Agents Fluoxetine medicine Animals Biological Psychiatry 5-HT receptor Dose-Response Relationship Drug Chemistry Tryptophan hydroxylase Receptor antagonist Ondansetron Antidepressive Agents 030227 psychiatry Lipid Peroxidation Serotonin Antagonists Oxidative stress medicine.drug |
| Zdroj: | Progress in neuro-psychopharmacologybiological psychiatry. 102 |
| ISSN: | 1878-4216 |
| Popis: | Monoaminergic and oxidative dysfunctions have been reported to play a role in depression. The present study investigated the antioxidant potential as well as the antidepressant-like action of 2-phenyl-3-(phenylselanyl)benzofuran (SeBZF1) in male Swiss mice. Time and dose-response curves were analyzed with the forced swim (FST) and tail suspension (TST) tests, in which SeBZF1 elicited antidepressant-like effects. Serotonergic mechanisms were investigated in the TST. The pre-administration of WAY100635 (selective 5-HT1A receptor antagonist, 0.1 mg/kg, subcutaneous route), ketanserin (5-HT2A/2C receptor antagonist, 1 mg/kg, intraperitoneal route, i.p.), and chlorophenylalaninemethyl ester (p-CPA) (selective tryptophan hydroxylase inhibitor, 100 mg/kg, i.p., for 4 days), but not of ondansetron (selective 5-HT3 receptor antagonist, 1 mg/kg, i.p.), abolished the antidepressant-like action of SeBZF1 (50 mg/kg, intragastric route, i.g.). Co-administration of sub-effective doses of SeBZF1 (1 mg/kg, i.g.) and fluoxetine (5 mg/kg, i.p., selective serotonin reuptake inhibitor) was effective in producing anti-immobility effects in the TST, revealing a synergistic effect. Besides, p-CPA induced hippocampal oxidative stress, characterized by a reduction of total thiols and lipoperoxidation, which was reversed by SeBZF1 (50 mg/kg). The in vitro screening of the antioxidant action of SeBZF1 in brain tissue reinforced these results. Lastly, SeBZF1 did not cause systemic toxicity at a high dose (300 mg/kg). In summary, the present study demonstrated that SeBZF1 exerted antidepressant-like action in male mice which appears to be mediated by the serotonergic system. Moreover, SeBZF1 elicited in vitro antioxidant action in brain tissue, attenuated the hippocampal oxidative damage induced by 5-HT depletion in mice and showed no toxic signs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect