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标题：Time-dependent activation of MAPK/Erk1/2 and Akt/GSK3 cascades: modulation by agomelatine
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作者：Laura Musazzi ; Mara Seguini ; Alessandra Mallei 等
期刊名称：BMC Neuroscience
印刷版ISSN：1471-2202
电子版ISSN：1471-2202
出版年度：2014
卷号：15
期号：1
页码：1
DOI：10.1186/s12868-014-0119-1
语种：English
出版社：BioMed Central
摘要：Background The novel antidepressant agomelatine, a melatonergic MT₁/MT₂ agonist combined with 5-HT_2c serotonin antagonist properties, showed antidepressant action in preclinical and clinical studies. There is a general agreement that the therapeutic action of antidepressants needs the activation of slow-onset adaptations in downstream signalling pathways finally regulating neuroplasticity. In the last several years, particular attention was given to cAMP-responsive element binding protein (CREB)-related pathways, since it was shown that chronic antidepressants increase CREB phosphorylation and transcriptional activity, through the activation of calcium/calmodulin-dependent (CaM) and mitogen activated protein kinase cascades (MAPK/Erk1/2). Aim of this work was to analyse possible effects of chronic agomelatine on time-dependent changes of different intracellular signalling pathways in hippocampus and prefrontal/frontal cortex of male rats. To this end, measurements were performed 1 h or 16 h after the last agomelatine or vehicle injection. Results We have found that in naïve rats chronic agomelatine, contrary to traditional antidepressants, did not increase CREB phosphorylation, but modulates the time-dependent regulation of MAPK/Erk1/2 and Akt/glycogen synthase kinase-3 (GSK-3) pathways. Conclusion Our results suggest that the intracellular molecular mechanisms modulated by chronic agomelatine may be partly different from those of traditional antidepressants and involve the time-dependent regulation of MAPK/Erk1/2 and Akt/GSK-3 signalling pathways. This could exert a role in the antidepressant efficacy of the drug.
关键词：Antidepressant ; Agomelatine ; Intracellular signalling ; Neuroplasticity ; Time-dependent regulation