Exploring the contribution of the dopaminergic and noradrenergic systems in the antidepressant-like action of 1-(2-(4-(4-ethylphenyl)-1H-1,2,3-triazol-1-yl)phenyl)ethanone in mice.
Marcelo Heinemann Presa, Marcia Juciele da Rocha, Kauane Nayara Bahr Ledebuhr, Narryman Pinto Zuge, Taís Barcelos Goulart, Diego Alves, Cristiani Folharini Bortolatto, César Augusto Brüning
{"title":"Exploring the contribution of the dopaminergic and noradrenergic systems in the antidepressant-like action of 1-(2-(4-(4-ethylphenyl)-1H-1,2,3-triazol-1-yl)phenyl)ethanone in mice.","authors":"Marcelo Heinemann Presa, Marcia Juciele da Rocha, Kauane Nayara Bahr Ledebuhr, Narryman Pinto Zuge, Taís Barcelos Goulart, Diego Alves, Cristiani Folharini Bortolatto, César Augusto Brüning","doi":"10.1016/j.bbr.2024.115390","DOIUrl":null,"url":null,"abstract":"<p><p>1-(2-(4-(4-ethylphenyl)-1H-1,2,3-triazol-1-yl)phenyl)ethanone (ETAP) is a novel hybrid compound containing 1,2,3-triazole and acetophenone. It exhibits antidepressant-like effects in male mice, linked to modulation of serotonergic receptors and monoamine oxidase A (MAO-A) inhibition. This study aimed to evaluate the involvement of the dopaminergic and noradrenergic systems, as well as MAO-B activity inhibition, in the antidepressant-like effect of ETAP in male mice, and to evaluate the antidepressant-like effect of ETAP in female mice. Male mice were treated with different dopaminergic and noradrenergic receptors antagonists 15 min before administering ETAP (1 mg/kg, intragastrically, i.g.). The tail suspension test (TST) was performed 30 minutes later. Different male mice were treated with ETAP (1 mg/kg, i.g.), and 30 minutes later, were euthanized to assess MAO-B activity in the prefrontal cortex and hippocampus. To evaluate the antidepressant-like of ETAP in female mice, ETAP (1 mg/kg, i.g.) was administered, followed by the TST and the forced swimming test (FST) 30 minutes later. The dopaminergic antagonists haloperidol (0.05 mg/kg, intraperitoneally, i.p.), SCH23390 (0.01 mg/kg, subcutaneously, s.c.), and sulpiride (50 mg/kg, i.p.), as well the noradrenergic antagonists prazosin (1 mg/kg, i.p.), yohimbine (1 mg/kg, i.p.), and propranolol (2 mg/kg, i.p.), prevented the antidepressant-like effect of ETAP in the TST. MAO-B activity was unaffected by ETAP in both the prefrontal cortex and hippocampus. ETAP (1 mg/kg, i.g.) induced a significant antidepressant-like effect in female mice in the TST and FST. These findings provide valuable insights into the antidepressant-like effect of ETAP, highlighting its potential for developing more effective depression treatments.</p>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":" ","pages":"115390"},"PeriodicalIF":2.6000,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Behavioural Brain Research","FirstCategoryId":"102","ListUrlMain":"https://doi.org/10.1016/j.bbr.2024.115390","RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
1-(2-(4-(4-ethylphenyl)-1H-1,2,3-triazol-1-yl)phenyl)ethanone (ETAP) is a novel hybrid compound containing 1,2,3-triazole and acetophenone. It exhibits antidepressant-like effects in male mice, linked to modulation of serotonergic receptors and monoamine oxidase A (MAO-A) inhibition. This study aimed to evaluate the involvement of the dopaminergic and noradrenergic systems, as well as MAO-B activity inhibition, in the antidepressant-like effect of ETAP in male mice, and to evaluate the antidepressant-like effect of ETAP in female mice. Male mice were treated with different dopaminergic and noradrenergic receptors antagonists 15 min before administering ETAP (1 mg/kg, intragastrically, i.g.). The tail suspension test (TST) was performed 30 minutes later. Different male mice were treated with ETAP (1 mg/kg, i.g.), and 30 minutes later, were euthanized to assess MAO-B activity in the prefrontal cortex and hippocampus. To evaluate the antidepressant-like of ETAP in female mice, ETAP (1 mg/kg, i.g.) was administered, followed by the TST and the forced swimming test (FST) 30 minutes later. The dopaminergic antagonists haloperidol (0.05 mg/kg, intraperitoneally, i.p.), SCH23390 (0.01 mg/kg, subcutaneously, s.c.), and sulpiride (50 mg/kg, i.p.), as well the noradrenergic antagonists prazosin (1 mg/kg, i.p.), yohimbine (1 mg/kg, i.p.), and propranolol (2 mg/kg, i.p.), prevented the antidepressant-like effect of ETAP in the TST. MAO-B activity was unaffected by ETAP in both the prefrontal cortex and hippocampus. ETAP (1 mg/kg, i.g.) induced a significant antidepressant-like effect in female mice in the TST and FST. These findings provide valuable insights into the antidepressant-like effect of ETAP, highlighting its potential for developing more effective depression treatments.
期刊介绍:
Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.