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  Chronic agomelatine treatment prevents comorbid depression in the post-status epilepticus model of acquired epilepsy through suppression of inflammatory signaling.

Tchekalarova, J., Atanasova, D. Y., Kortenska, L., Atanasova, M., & Lazarov, N. (2018). Chronic agomelatine treatment prevents comorbid depression in the post-status epilepticus model of acquired epilepsy through suppression of inflammatory signaling. Neurobiology of Disease, 115, 127-144. doi:10.1016/j.nbd.2018.04.005.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0001-69DA-4 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-BC4A-7
Genre: Journal Article

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Tchekalarova, J., Author
Atanasova, D. Y.1, Author              
Kortenska, L., Author
Atanasova, M., Author
Lazarov, N., Author
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1Department of Genes and Behavior, MPI for Biophysical Chemistry, Max Planck Society, ou_persistent34              

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Free keywords: Agomelatine; Epilepsy; Depression; Interleukin-1 beta; Neuroglia; Wistar rat
 Abstract: Inflammatory signal molecules are suggested to be involved in the mechanism underlying comorbid depression in epilepsy. In the present study, we tested the hypothesis that the novel antidepressant agomelatine, a potent melatonin MT1, and MT2 receptor agonist and serotonin 5FIT(2c) receptor antagonist, can prevent depressive symptoms developed during the chronic epileptic phase by suppressing an inflammatory response. Chronic treatment with agomelatine (40 mg/kg, i.p.) was initiated an hour after the kainate acid (KA)-induced status epilepticus (SE) and maintained for a period of 10 weeks in Wistar rats, Registration of spontaneous motor seizures was performed through a video (24 h/day) and EEG monitoring. Antidepressant activity of agomelatine was explored in the splash test, sucrose preference test (SPT) and forced swimming test (FST) while anxiolytic effect was observed through the novelty suppression-feeding test (NSFT) during chronic phase in epileptic rats. The frequency of motor seizures detected by video and EEG recording did not differ between vehicle and Ago group. Rats with registered spontaneous motor seizures showed symptoms typical for depressive behavior that included decreased grooming, anhedonia during the dark period and hopeless-like behavior. Epileptic rats exhibited also anxiety with novelty-induced hypophagia. This behavioral deficit correlated with increased signal markers of inflammation (plasma levels of interleukin (IL)-1 beta and activated glia in brain), while plasma corticosterone levels were not changed. Agomelatine treatment during epileptogenesis exerted a clear antidepressant effect by suppressing all behavioral hallmarks, reducing plasma IL-1 beta levels and preventing microgliosis and astrogliosis in specific limbic regions. The present results suggest that agomelatine treatment starting after SE can provide an effective therapy of comorbid depression in chronic epileptic condition through suppression of inflammatory signaling.

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Language(s): eng - English
 Dates: 2018-04-102018-07
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.nbd.2018.04.005
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Title: Neurobiology of Disease
Source Genre: Journal
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Pages: - Volume / Issue: 115 Sequence Number: - Start / End Page: 127 - 144 Identifier: -