6533b829fe1ef96bd128a3fa

RESEARCH PRODUCT

Role(s) of the 5-HT2C receptor in the development of maximal dentate activation in the hippocampus of anesthetized rats.

Gergely OrbanFabio BucchieriPhilippe De DeurwaerdèreBenigno ArcangeloAntonella Marino GammazzaRoberto ColangeliMauro PessiaMassimo PierucciCristiano BombardiGiuseppe Di GiovanniGiuseppe Di GiovanniCristoforo PomaraCristoforo PomaraIlse Julia Smolders

subject

MaleSerotonin receptorsmedicine.medical_specialtyGlutamate decarboxylaseDentate gyrus; Depression; GABA; Memory; Serotonergic2c drugs; Serotonin receptors; Temporal lobe epilepsyHippocampusHippocampal formationDentate gyruEpileptogenesisSettore BIO/09 - FisiologiaHippocampusDentate gyrus; Depression; GABA; Memory;LorcaserinRats Sprague-DawleySerotonergic 2c drugGABAEpilepsyMemoryDentate gyrus; Depression; GABA; Memory; Serotonin receptors; Temporal lobe epilepsyPhysiology (medical)Internal medicinemedicineReceptor Serotonin 5-HT2CAnimalsDentate gyrusPharmacology (medical)Serotonin receptorTemporal lobe epilepsyPharmacologyDepressionChemistryDentate gyrusDentate gyrus;Depression; GABA; Memory; Serotonergic2c drugs; Serotonin receptors; Temporal lobe epilepsyOriginal Articlesmedicine.diseaseRats5-HT2C receptorPsychiatry and Mental healthEndocrinologyDepression MentalEpilepsy Temporal LobeDentate GyrusSerotonergic2c drugAnesthetics IntravenousSerotonin 5-HT2 Receptor Agonistsmedicine.drug

description

Aims: Substantial evidence indicates that 5-HT2C receptors are involved in the control of neuronal network excitability and in seizure pathophysiology. Here, we have addressed the relatively unexplored relationship between temporal lobe epilepsy (TLE), the most frequent type of intractable epilepsy, and 5-HT2CRs. Methods: In this study, we investigated this issue using a model of partial complex (limbic) seizures in urethane-anesthetized rat, based on the phenomenon of maximal dentate activation (MDA) using 5-HT2C compounds, electrophysiology, immunohistochemistry, and western blotting techniques. Results: The 5-HT2C agonists mCPP (1 mg/kg, i.p) and lorcaserin (3 mg/kg, i.p), but not RO60-0175 (1–3 mg/kg i.p.), were antiepileptogenic reducing the MDA response duration. The selective 5-HT2C antagonist SB242084 (2 mg/kg, i.p) unveiled antiepileptogenic effects of RO60- 0175 (3 mg/kg, i.p) but did not alter those induced by mCPP and lorcaserin. Compared with control rats, electrically stimulated rats showed an increase in glutamic acid decarboxylase levels and a heterogeneous decrease in 5-HT2CR immunoreactivity in different hippocampal areas. Conclusions: In our animal model of TLE, mCPP and lorcaserin were anticonvulsant; likely acting on receptor subtypes other than 5-HT2C. Epileptogenesis induced early adaptive changes and reorganization in the 5-HT2CR and GABA systems.

yearjournalcountryeditionlanguage
2014-06-17
10.1111/cns.12285http://hdl.handle.net/11391/1318710