Larissa Sander Magalhães , Dianer Nornberg Strelow , Mariana Parron Paim , Taís da Silva Teixeira Rech , Letícia Devantier Krüger , Antonio Luiz Braga , José Sebastião Santos Neto , César Augusto Brüning , Cristiani Folharini Bortolatto
{"title":"3-(4-甲氧基苯基)selanyl)-2-苯基苯并呋喃(SeBZF3)对小鼠的类似焦虑作用:5-羟色胺能系统的可能贡献。","authors":"Larissa Sander Magalhães , Dianer Nornberg Strelow , Mariana Parron Paim , Taís da Silva Teixeira Rech , Letícia Devantier Krüger , Antonio Luiz Braga , José Sebastião Santos Neto , César Augusto Brüning , Cristiani Folharini Bortolatto","doi":"10.1016/j.pbb.2023.173651","DOIUrl":null,"url":null,"abstract":"<div><p><span>Anxiety disorders, characterized by high prevalence rates, cause psychiatric disabilities and are related to impairments in serotoninergic system function. Frequent anxiety recurrence, resistance, and drug adverse effects have driven searches for new therapies. We initially evaluated the anxiolytic-like activity of 3-selanyl-benzo[</span><em>b</em>]furan compounds (SeBZF<strong>1–5</strong><span>) (50 mg/kg, i.g.) in male Swiss mice using the light-dark test (LDT). The compound 3-((4-methoxyphenyl)selanyl)-2-phenylbenzofuran (SeBZF</span><strong>3</strong><span>) exhibited anxiolytic-like activity. SeBZF</span><strong>3</strong> anxiolytic-like effects were also observed in the novelty-suppressed feeding test (NSFT) (50 mg/kg) and elevated plus-maze test (EPMT) (25 and 50 mg/kg). In the EPMT, anxiolytic-like effects of SeBZF<strong>3</strong> (50 mg/kg) were abolished by pretreatment with <em>p</em><span>-chlorophenylalanine, a selective tryptophan hydroxylase<span> inhibitor (100 mg/kg, i.p. for 4 days), suggesting the involvement of serotonergic mechanisms. Furthermore, we conducted experiments to investigate the synergistic effects of SeBZF</span></span><strong>3</strong><span><span><span><span> subeffective doses (5 mg/kg, i.g.) in combination with fluoxetine (a </span>selective serotonin reuptake inhibitor, 5 mg/kg, i.p.) or </span>buspirone (a </span>partial agonist of the 5-HT</span><sub>1A</sub> receptor, 2 mg/kg, i.p.). This coadministration resulted in pronounced synergistic effects. We also examined the effects of repeated oral treatment with SeBZF<strong>3</strong> at doses of 1 and 5 mg/kg over 14 days and both reduced anxiety signals. <em>In vitro</em> and <em>ex vivo</em> findings revealed that SeBZF<strong>3</strong> inhibited cerebral MAO-A activity. These findings collectively imply the potential involvement of serotonergic mechanisms in the anxiolytic-like activity of SeBZF<strong>3</strong><span> in mice. These data offer contributions to the research field of organoselenium compounds and anxiolytics, encouraging the broadening of the search for new effective drugs while offering improved side effect profiles.</span></p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"232 ","pages":"Article 173651"},"PeriodicalIF":3.3000,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Anxiolytic-like action of 3-((4-methoxyphenyl)selanyl)-2-phenylbenzofuran (SeBZF3) in mice: A possible contribution of the serotonergic system\",\"authors\":\"Larissa Sander Magalhães , Dianer Nornberg Strelow , Mariana Parron Paim , Taís da Silva Teixeira Rech , Letícia Devantier Krüger , Antonio Luiz Braga , José Sebastião Santos Neto , César Augusto Brüning , Cristiani Folharini Bortolatto\",\"doi\":\"10.1016/j.pbb.2023.173651\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span>Anxiety disorders, characterized by high prevalence rates, cause psychiatric disabilities and are related to impairments in serotoninergic system function. Frequent anxiety recurrence, resistance, and drug adverse effects have driven searches for new therapies. We initially evaluated the anxiolytic-like activity of 3-selanyl-benzo[</span><em>b</em>]furan compounds (SeBZF<strong>1–5</strong><span>) (50 mg/kg, i.g.) in male Swiss mice using the light-dark test (LDT). The compound 3-((4-methoxyphenyl)selanyl)-2-phenylbenzofuran (SeBZF</span><strong>3</strong><span>) exhibited anxiolytic-like activity. SeBZF</span><strong>3</strong> anxiolytic-like effects were also observed in the novelty-suppressed feeding test (NSFT) (50 mg/kg) and elevated plus-maze test (EPMT) (25 and 50 mg/kg). In the EPMT, anxiolytic-like effects of SeBZF<strong>3</strong> (50 mg/kg) were abolished by pretreatment with <em>p</em><span>-chlorophenylalanine, a selective tryptophan hydroxylase<span> inhibitor (100 mg/kg, i.p. for 4 days), suggesting the involvement of serotonergic mechanisms. Furthermore, we conducted experiments to investigate the synergistic effects of SeBZF</span></span><strong>3</strong><span><span><span><span> subeffective doses (5 mg/kg, i.g.) in combination with fluoxetine (a </span>selective serotonin reuptake inhibitor, 5 mg/kg, i.p.) or </span>buspirone (a </span>partial agonist of the 5-HT</span><sub>1A</sub> receptor, 2 mg/kg, i.p.). This coadministration resulted in pronounced synergistic effects. We also examined the effects of repeated oral treatment with SeBZF<strong>3</strong> at doses of 1 and 5 mg/kg over 14 days and both reduced anxiety signals. <em>In vitro</em> and <em>ex vivo</em> findings revealed that SeBZF<strong>3</strong> inhibited cerebral MAO-A activity. These findings collectively imply the potential involvement of serotonergic mechanisms in the anxiolytic-like activity of SeBZF<strong>3</strong><span> in mice. These data offer contributions to the research field of organoselenium compounds and anxiolytics, encouraging the broadening of the search for new effective drugs while offering improved side effect profiles.</span></p></div>\",\"PeriodicalId\":19893,\"journal\":{\"name\":\"Pharmacology Biochemistry and Behavior\",\"volume\":\"232 \",\"pages\":\"Article 173651\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2023-10-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmacology Biochemistry and Behavior\",\"FirstCategoryId\":\"102\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0091305723001387\",\"RegionNum\":3,\"RegionCategory\":\"心理学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BEHAVIORAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacology Biochemistry and Behavior","FirstCategoryId":"102","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0091305723001387","RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
Anxiolytic-like action of 3-((4-methoxyphenyl)selanyl)-2-phenylbenzofuran (SeBZF3) in mice: A possible contribution of the serotonergic system
Anxiety disorders, characterized by high prevalence rates, cause psychiatric disabilities and are related to impairments in serotoninergic system function. Frequent anxiety recurrence, resistance, and drug adverse effects have driven searches for new therapies. We initially evaluated the anxiolytic-like activity of 3-selanyl-benzo[b]furan compounds (SeBZF1–5) (50 mg/kg, i.g.) in male Swiss mice using the light-dark test (LDT). The compound 3-((4-methoxyphenyl)selanyl)-2-phenylbenzofuran (SeBZF3) exhibited anxiolytic-like activity. SeBZF3 anxiolytic-like effects were also observed in the novelty-suppressed feeding test (NSFT) (50 mg/kg) and elevated plus-maze test (EPMT) (25 and 50 mg/kg). In the EPMT, anxiolytic-like effects of SeBZF3 (50 mg/kg) were abolished by pretreatment with p-chlorophenylalanine, a selective tryptophan hydroxylase inhibitor (100 mg/kg, i.p. for 4 days), suggesting the involvement of serotonergic mechanisms. Furthermore, we conducted experiments to investigate the synergistic effects of SeBZF3 subeffective doses (5 mg/kg, i.g.) in combination with fluoxetine (a selective serotonin reuptake inhibitor, 5 mg/kg, i.p.) or buspirone (a partial agonist of the 5-HT1A receptor, 2 mg/kg, i.p.). This coadministration resulted in pronounced synergistic effects. We also examined the effects of repeated oral treatment with SeBZF3 at doses of 1 and 5 mg/kg over 14 days and both reduced anxiety signals. In vitro and ex vivo findings revealed that SeBZF3 inhibited cerebral MAO-A activity. These findings collectively imply the potential involvement of serotonergic mechanisms in the anxiolytic-like activity of SeBZF3 in mice. These data offer contributions to the research field of organoselenium compounds and anxiolytics, encouraging the broadening of the search for new effective drugs while offering improved side effect profiles.
期刊介绍:
Pharmacology Biochemistry & Behavior publishes original reports in the areas of pharmacology and biochemistry in which the primary emphasis and theoretical context are behavioral. Contributions may involve clinical, preclinical, or basic research. Purely biochemical or toxicology studies will not be published. Papers describing the behavioral effects of novel drugs in models of psychiatric, neurological and cognitive disorders, and central pain must include a positive control unless the paper is on a disease where such a drug is not available yet. Papers focusing on physiological processes (e.g., peripheral pain mechanisms, body temperature regulation, seizure activity) are not accepted as we would like to retain the focus of Pharmacology Biochemistry & Behavior on behavior and its interaction with the biochemistry and neurochemistry of the central nervous system. Papers describing the effects of plant materials are generally not considered, unless the active ingredients are studied, the extraction method is well described, the doses tested are known, and clear and definite experimental evidence on the mechanism of action of the active ingredients is provided.