Agomelatine protects against neuronal damage without preventing epileptogenesis in the kainate model of temporal lobe epilepsy
Recent studies about the novel antidepressant agomelatine, which is a mixed MT1 and MT2 melatonin receptor agonist and 5HT2C serotonin receptor antagonist possessing an anticonvulsant and neuroprotective action, suggest that it may have potential to contribute against epileptogenesis and epilepsy-in...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-08-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996117300918 |
| _version_ | 1819159789602603008 |
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| author | Jana Tchekalarova Dimitrinka Atanasova Zlatina Nenchovska Milena Atanasova Lidia Kortenska Rumyana Gesheva Nikolai Lazarov |
| author_facet | Jana Tchekalarova Dimitrinka Atanasova Zlatina Nenchovska Milena Atanasova Lidia Kortenska Rumyana Gesheva Nikolai Lazarov |
| author_sort | Jana Tchekalarova |
| collection | DOAJ |
| description | Recent studies about the novel antidepressant agomelatine, which is a mixed MT1 and MT2 melatonin receptor agonist and 5HT2C serotonin receptor antagonist possessing an anticonvulsant and neuroprotective action, suggest that it may have potential to contribute against epileptogenesis and epilepsy-induced memory impairment. In order to ascertain whether protection of some brain structures could suppress epileptogenesis, in the present study, we evaluated the effect of chronic post-status treatment with agomelatine on epileptogenesis, behavioral and neuronal damage induced by kainate acid (KA) status epilepticus (SE). Agomelatine/vehicle treatment (40 mg/kg, i.p.) started one hour after SE and continued up to 10 weeks in Wistar rats. Latency for onset of spontaneous motor seizures (SMS) and their frequency was detected by a 24-h video-recording. Locomotor activity, anxiety and hippocampus-dependent spatial memory in open field (OF), elevated plus maze (EPM), light-dark test (LDT) and radial arm maze (RAM) test, respectively, were evaluated during the last two weeks after SE. Agomelatine significantly decreased the latency for onset of SMS and increased the seizure frequency during the 2nd and the 3rd week of treatment. The MT1 and MT2 receptor agonist and serotonin 5HT2C receptor antagonist exacerbated the KA-induced hyperlocomotion and impulsive behavior and it was unable to prevent spatial memory impairment of epileptic rats. However, agomelatine induced a neuroprotection in the dorsal hippocampus, specifically in the CA1, septal CA2 and partially in the CA3c region, the hilus of the dentate gyrus, piriform cortex and septo-temporal and temporal basolateral amygdala. Our findings suggest that the beneficial impact against SE-induced neuronal loss exerted by agomelatine is not crucial for the suppression of epileptogenesis and its deleterious consequences in KA model of temporal lobe epilepsy. |
| first_indexed | 2024-12-22T16:46:08Z |
| format | Article |
| id | doaj.art-a88c9399598846bf80d5ffe433037908 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-22T16:46:08Z |
| publishDate | 2017-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-a88c9399598846bf80d5ffe4330379082022-12-21T18:19:43ZengElsevierNeurobiology of Disease1095-953X2017-08-01104114Agomelatine protects against neuronal damage without preventing epileptogenesis in the kainate model of temporal lobe epilepsyJana Tchekalarova0Dimitrinka Atanasova1Zlatina Nenchovska2Milena Atanasova3Lidia Kortenska4Rumyana Gesheva5Nikolai Lazarov6Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria; Corresponding author at: Institute of Neurobiology, Acad. G. Bonchev Str., Bl. 23, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria.Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria; Department of Anatomy, Faculty of Medicine, Trakia University, Stara Zagora 6003, BulgariaInstitute of Neurobiology, Bulgarian Academy of Sciences, Sofia 1113, BulgariaDepartment of Biology, Medical University of Pleven, Pleven 5800, BulgariaInstitute of Neurobiology, Bulgarian Academy of Sciences, Sofia 1113, BulgariaInstitute of Neurobiology, Bulgarian Academy of Sciences, Sofia 1113, BulgariaInstitute of Neurobiology, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria; Department of Anatomy and Histology, Medical University of Sofia, Sofia 1431, BulgariaRecent studies about the novel antidepressant agomelatine, which is a mixed MT1 and MT2 melatonin receptor agonist and 5HT2C serotonin receptor antagonist possessing an anticonvulsant and neuroprotective action, suggest that it may have potential to contribute against epileptogenesis and epilepsy-induced memory impairment. In order to ascertain whether protection of some brain structures could suppress epileptogenesis, in the present study, we evaluated the effect of chronic post-status treatment with agomelatine on epileptogenesis, behavioral and neuronal damage induced by kainate acid (KA) status epilepticus (SE). Agomelatine/vehicle treatment (40 mg/kg, i.p.) started one hour after SE and continued up to 10 weeks in Wistar rats. Latency for onset of spontaneous motor seizures (SMS) and their frequency was detected by a 24-h video-recording. Locomotor activity, anxiety and hippocampus-dependent spatial memory in open field (OF), elevated plus maze (EPM), light-dark test (LDT) and radial arm maze (RAM) test, respectively, were evaluated during the last two weeks after SE. Agomelatine significantly decreased the latency for onset of SMS and increased the seizure frequency during the 2nd and the 3rd week of treatment. The MT1 and MT2 receptor agonist and serotonin 5HT2C receptor antagonist exacerbated the KA-induced hyperlocomotion and impulsive behavior and it was unable to prevent spatial memory impairment of epileptic rats. However, agomelatine induced a neuroprotection in the dorsal hippocampus, specifically in the CA1, septal CA2 and partially in the CA3c region, the hilus of the dentate gyrus, piriform cortex and septo-temporal and temporal basolateral amygdala. Our findings suggest that the beneficial impact against SE-induced neuronal loss exerted by agomelatine is not crucial for the suppression of epileptogenesis and its deleterious consequences in KA model of temporal lobe epilepsy.http://www.sciencedirect.com/science/article/pii/S0969996117300918AgomelatineKainateEpileptogenesisBehaviorNeuronal loss |
| spellingShingle | Jana Tchekalarova Dimitrinka Atanasova Zlatina Nenchovska Milena Atanasova Lidia Kortenska Rumyana Gesheva Nikolai Lazarov Agomelatine protects against neuronal damage without preventing epileptogenesis in the kainate model of temporal lobe epilepsy Neurobiology of Disease Agomelatine Kainate Epileptogenesis Behavior Neuronal loss |
| title | Agomelatine protects against neuronal damage without preventing epileptogenesis in the kainate model of temporal lobe epilepsy |
| title_full | Agomelatine protects against neuronal damage without preventing epileptogenesis in the kainate model of temporal lobe epilepsy |
| title_fullStr | Agomelatine protects against neuronal damage without preventing epileptogenesis in the kainate model of temporal lobe epilepsy |
| title_full_unstemmed | Agomelatine protects against neuronal damage without preventing epileptogenesis in the kainate model of temporal lobe epilepsy |
| title_short | Agomelatine protects against neuronal damage without preventing epileptogenesis in the kainate model of temporal lobe epilepsy |
| title_sort | agomelatine protects against neuronal damage without preventing epileptogenesis in the kainate model of temporal lobe epilepsy |
| topic | Agomelatine Kainate Epileptogenesis Behavior Neuronal loss |
| url | http://www.sciencedirect.com/science/article/pii/S0969996117300918 |
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