ERK1/2 phosphorylation is involved in the antidepressant-like action of 2,5-dipheny1-3-(4-fluorophenylseleno)-selenophene in mice

作者：Gai Bibiana Mozzaquatro; Sanna Maria Domenica; Stein Andre Luiz; Zeni Gilson; Galeotti Nicoletta; Nogueira Cristina Wayne^*

来源：European Journal of Pharmacology, 2014, 736: 44-54.

DOI：10.1016/j.ejphar.2014.04.033

• Selenium
• Selenophene
• Mice
• Antidepressant-like
• ERIC phosphorylation

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, timecourse and dose-response effect of H-DPS, CH3-DPS, CI-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 anti-despair behavior induced by CI-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 doseresponse effect, all compounds reduced immobility time and increased latency for the first episode of immobility at a dose of 50 mg/1<g. In addition, F-DPS also showed antidepressant-like action at a dose of 25 mg/kg, whilst H-DPS, CH3-DPS, CI-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.

• 出版日期2014-8-5