title: Role(s) of the 5-HT2C receptor in the development of maximal dentate activation in the hippocampus of anesthetized rats.
abstract: OBJECTIVE
  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.
authors.affiliation: Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Università degli Studi di Palermo, Palermo, Italy; Istituto Euro-Mediterraneo di Scienza e Tecnologia (IEMEST), Palermo, Italy.
authors.forename: Gergely
authors.initials: G
authors.lastname: Orban
authors.forename: Cristiano
authors.initials: C
authors.lastname: Bombardi
authors.forename: Antonella
authors.initials: A
authors.lastname: Marino Gammazza
authors.forename: Roberto
authors.initials: R
authors.lastname: Colangeli
authors.forename: Massimo
authors.initials: M
authors.lastname: Pierucci
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Pomara
authors.forename: Mauro
authors.initials: M
authors.lastname: Pessia
authors.forename: Fabio
authors.initials: F
authors.lastname: Bucchieri
authors.forename: Arcangelo
authors.initials: A
authors.lastname: Benigno
authors.forename: Benigno
authors.initials: B
authors.lastname: Arcangelo
authors.forename: Ilse
authors.initials: I
authors.lastname: Smolders
authors.forename: Philippe
authors.initials: P
authors.lastname: De Deurwaerdère
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Giovanni
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology*; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018686:Anesthetics, Intravenous; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists
keywords: Dentate gyrus; Depression; GABA; Memory; Serotonergic2c drugs; Serotonin receptors; Temporal lobe epilepsy