TY - JOUR
T1 - Role(s) of the 5-HT2C receptor in the development of maximal dentate activation in the hippocampus of anesthetized rats
AU - Orban, Gergely
AU - Bombardi, Cristiano
AU - Marino Gammazza, Antonella
AU - Colangeli, Roberto
AU - Pierucci, Massimo
AU - Pomara, Cristoforo
AU - Pessia, Mauro
AU - Bucchieri, Fabio
AU - Arcangelo, Benigno
AU - Smolders, Ilse
AU - De Deurwaerdère, Philippe
AU - Di Giovanni, Giuseppe
PY - 2014/7
Y1 - 2014/7
N2 - 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.
AB - 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.
KW - Dentate gyrus
KW - Depression
KW - GABA
KW - Memory
KW - Serotonin receptors
KW - Temporal lobe epilepsy
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U2 - 10.1111/cns.12285
DO - 10.1111/cns.12285
M3 - Article
C2 - 24935789
AN - SCOPUS:84902478392
SN - 1755-5930
VL - 20
SP - 651
EP - 661
JO - CNS Neuroscience and Therapeutics
JF - CNS Neuroscience and Therapeutics
IS - 7
ER -