Chronic stress and antidepressant agomelatine induce region‐specific changes in synapsin I expression in the rat brain
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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 (SynI), 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 SynI. Chronic footshock and agomelatine induced region‐specific changes in SynI expression. Whereas chronic stress increased total SynI expression in all layers of the medial prefrontal cortex, agomelatine treatment abolished some of these effects. Furthermore, chronic agomelatine administration decreased total SynI expression in the hippocampal subregions of both stressed and nonstressed rats. Importantly, chronic stress decreased the fraction of phosphorylated SynI 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 SynI expression and its phosphorylation. Moreover, agomelatine partially counteracts the stress effects on SynI, suggesting a modulation of synaptic function by this antidepressant. © 2011 Wiley‐Liss, Inc.
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- Authors
- Dagyte, G., Luiten, P. G., De Jager, T., Gabriel, C., Mocaër, E., Den Boer, J. A., & Van der Zee, E. A.
- Affiliations
- University of Groningen (NL)
- Servier (France) (FR)
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 2011-06-17
- Volume
- 89
- Issue
- 10
- Pages
- 1646-1657
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- OpenAlex
- W2114426673
- Cited by
- 32
- References
- 71
- Citations by year
- 2022: 5 · 2021: 4 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 6 · 2013: 4 · 2012: 5
- FWCI
- 3.75
- Type
- journal article
- Language
- en
- Open access
- green
- research.rug.nl
- Licence
- Locations
- Journal of Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- agomelatine, chronic stress, synapsin I, synapsin I phosphorylation, antidepressants, depression, footshock stress, medial prefrontal cortex, hippocampus, dentate gyrus, synaptic plasticity, 5-HT2C receptor antagonist
- MeSH terms
- Acetamides, Animals, Antidepressive Agents, Brain Chemistry, Chronic Disease, Depressive Disorder, Disease Models, Animal, Male, Naphthalenes, Stress, Psychological, Synapsins, Rats, Wistar, Rats
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