title: ERK1/2 phosphorylation is involved in the antidepressant-like action of 2,5-diphenyl-3-(4-fluorophenylseleno)-selenophene in mice.
abstract: We investigated the antidepressant-like action of 5 compounds belonging to the selenophene class. The involvement of ERK and CREB activation in this action was also demonstrated. In the experiment 1, time-course and dose-response effect of H-DPS, CH3-DPS, Cl-DPS, F-DPS and CF3-DPS were accompanied in the mouse forced swimming test (FST). Firstly, animals received compounds at a dose of 50mg/kg, by intragastric (i.g.) route, at different times (15-240 min) before test. Results showed that the peak of maximum anti-despair behavior induced by Cl-DPS, F-DPS and CF3-DPS was at 30 min; maximum effect of H-DPS and CH3-DPS was found at 60 min, which was maintained until 120 min. Regarding dose-response effect, all compounds reduced immobility time and increased latency for the first episode of immobility at a dose of 50mg/kg. In addition, F-DPS also showed antidepressant-like action at a dose of 25mg/kg, whilst H-DPS, CH3-DPS, Cl-DPS and CF3-DPS were not effective at lower doses. Thus, F-DPS was chosen for further investigation of its mechanism of action. Experiment 2 showed that treatment of animals with F-DPS (50 mg/kg, i.g.) significantly increased phosphorylated ERK1/2 levels in the prefrontal cortex and hippocampus; however, pCREB levels were not affected. Additionally, in the experiment 3 anti-immobility effect of F-DPS was completely blocked by pretreatment of animals with PD 98,059, an inhibitor of ERK phosphorylation, suggesting that ERK signalling activation is involved in its antidepressant-like action in mice. Together our data appoint F-DPS as a promising molecule for the development of a new antidepressant therapy.
authors.affiliation: Laboratory of Synthesis, Reactivity and Pharmacological and Toxicological Evaluation of Organochalcogens, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria CEP 97105-900, RS, Brazil.
authors.forename: Bibiana Mozzaquatro
authors.initials: BM
authors.lastname: Gai
authors.affiliation: Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Viale G. Pieraccini 6, I-50139 Florence, Italy.
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Sanna
authors.affiliation: Laboratory of Synthesis, Reactivity and Pharmacological and Toxicological Evaluation of Organochalcogens, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria CEP 97105-900, RS, Brazil.
authors.forename: André Luiz
authors.initials: AL
authors.lastname: Stein
authors.affiliation: Laboratory of Synthesis, Reactivity and Pharmacological and Toxicological Evaluation of Organochalcogens, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria CEP 97105-900, RS, Brazil.
authors.forename: Gilson
authors.initials: G
authors.lastname: Zeni
authors.affiliation: Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Viale G. Pieraccini 6, I-50139 Florence, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Galeotti
authors.affiliation: Laboratory of Synthesis, Reactivity and Pharmacological and Toxicological Evaluation of Organochalcogens, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria CEP 97105-900, RS, Brazil. Electronic address: criswn@quimica.ufsm.br.
authors.forename: Cristina Wayne
authors.initials: CW
authors.lastname: Nogueira
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019417:Hindlimb Suspension; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D013550:Swimming
chemical_list: C000594800:2,5-diphenyl-3-(4-fluorophenylseleno)-selenophene; D000928:Antidepressive Agents; D016566:Organoselenium Compounds; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Antidepressant-like; ERK phosphorylation; Mice; Selenium; Selenophene