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

Gergely Orban, Cristiano Bombardi, Antonella Marino Gammazza, Roberto Colangeli, Massimo Pierucci, Cristoforo Pomara, Mauro Pessia, Fabio Bucchieri, Benigno Arcangelo, Ilse Smolders, Philippe De Deurwaerdère, Giuseppe Di Giovanni

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)651-661
Number of pages11
JournalCNS Neuroscience and Therapeutics
Volume20
Issue number7
DOIs
Publication statusPublished - Jul 2014
Externally publishedYes

Keywords

  • Dentate gyrus
  • Depression
  • GABA
  • Memory
  • Serotonin receptors
  • Temporal lobe epilepsy

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Physiology (medical)
  • Pharmacology (medical)

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