We investigated the antidepressant-like action of five 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 50 mg/kg, by intragastric (i.g.) route, at different times (15-240 min) before test. Results showed that the peak of maximum antidespair 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 50 mg/kg. In addition, F-DPS also showed antidepressant-like action at a dose of 25 mg/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 signaling 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.
ERK1/2 phosphorylation is involved in the antidepressant-like action of 2,5-diphenyl-3-(4-fluorophenylseleno)-selenophene in mice / Bibiana Mozzaquatro Gai;Maria Domenica Sanna;Andr? Luiz Stein;Gilson Zeni;Nicoletta Galeotti;Cristina Wayne Nogueira. - In: EUROPEAN JOURNAL OF PHARMACOLOGY. - ISSN 0014-2999. - STAMPA. - 736:(2014), pp. 44-54. [10.1016/j.ejphar.2014.04.033]
ERK1/2 phosphorylation is involved in the antidepressant-like action of 2,5-diphenyl-3-(4-fluorophenylseleno)-selenophene in mice
SANNA, MARIA DOMENICA;GALEOTTI, NICOLETTA;
2014
Abstract
We investigated the antidepressant-like action of five 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 50 mg/kg, by intragastric (i.g.) route, at different times (15-240 min) before test. Results showed that the peak of maximum antidespair 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 50 mg/kg. In addition, F-DPS also showed antidepressant-like action at a dose of 25 mg/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 signaling 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.File | Dimensione | Formato | |
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139.Eur J Pharmacol 2014.pdf
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