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Chronic stress and antidepressant agomelatine induce region-specific changes in synapsin I expression in the rat brain

Dagyte, G., Luiten, P. G., de Jager, T., Gabriel, C., Mocaer, E., den Boer, J. A. & van der Zee, E. A., Oct-2011, In : Journal of Neuroscience Research. 89, 10, p. 1646-1657 12 p.

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  • Chronic stress and antidepressant agomelatine induce region-specific

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The antidepressant agomelatine acts as a melatonergic receptor (MT(1)/MT(2)) agonist and 5-HT(2C) receptor antagonist. Agomelatine has demonstrated efficacy in treating depression, but its neurobiological effects merit further investigation. Preclinical studies reported that agomelatine enhances adult hippocampal neurogenesis and increases expression of several neuroplasticity-associated molecules. Recently, we showed that agomelatine normalizes hippocampal neuronal activity and promotes neurogenesis in the stress-compromised brain. To characterize further the effects of this antidepressant in the stressed brain, here we investigated whether it induces changes in the expression of synapsin I (Synl), a regulator of synaptic transmission and plasticity. Adult male rats were subjected to daily footshock stress and agomelatine treatment for 3 weeks. Their brains were subsequently stained for total and phosphorylated Synl. Chronic footshock and agomelatine induced region-specific changes in Synl expression. Whereas chronic stress increased total Synl expression in all layers of the medial prefrontal cortex, agomelatine treatment abolished some of these effects. Furthermore, chronic agomelatine administration decreased total Synl expression in the hippocampal subregions of both stressed and nonstressed rats. Importantly, chronic stress decreased the fraction of phosphorylated Synl in all layers of the medial prefrontal cortex as well as selectively in the outer and middle molecular layers of the hippocampal dentate gyrus. These stress effects were at least partially abolished by agomelatine. Altogether, our data show that chronic stress and agomelatine treatment induce region-specific changes in Synl expression and its phosphorylation. Moreover, agomelatine partially counteracts the stress effects on Synl, suggesting a modulation of synaptic function by this antidepressant. (C) 2011 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)1646-1657
Number of pages12
JournalJournal of Neuroscience Research
Volume89
Issue number10
Publication statusPublished - Oct-2011

    Keywords

  • affective disorders, chronic footshock stress, depression, synaptic plasticity, CHRONIC MILD STRESS, SYNAPTIC VESICLE PHOSPHOPROTEINS, TERMINAL-SPECIFIC PHOSPHOPROTEIN, MAJOR DEPRESSIVE DISORDER, MEDIAL PREFRONTAL CORTEX, DENTATE GYRUS, NEUROTRANSMITTER RELEASE, NEUROTROPHIC FACTORS, MELATONIN RECEPTORS, RESTRAINT STRESS

ID: 5397184