Agomelatine protects against neuronal damage without preventing epileptogenesis in the kainate model of temporal lobe epilepsy.
Neurobiol Dis
; 104: 1-14, 2017 Aug.
Article
em En
| MEDLINE
| ID: mdl-28438504
ABSTRACT
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 (40mg/kg, i.p.) started one hour after SE and continued up to 10weeks 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.
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MEDLINE
Assunto principal:
Epilepsia do Lobo Temporal
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Hipocampo
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Acetamidas
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Neurônios
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article