TY - JOUR
T1 - High dose of 8-OH-DPAT decreases maximal dentate gyrus activation and facilitates granular cell plasticity in vivo
AU - Orban, Gergely
AU - Pierucci, Massimo
AU - Benigno, Arcangelo
AU - Pessia, Mauro
AU - Galati, Salvatore
AU - Valentino, Mario
AU - Muscat, Richard
AU - Di Giovanni, Giuseppe
N1 - Funding Information:
Acknowledgments this study was supported by University of Malta research funding scheme, coordinator G. Di Giovanni. G.O. is supported by MIUR, Italy.
PY - 2013/10
Y1 - 2013/10
N2 - Although several studies have emphasized a crucial role for the serotonergic system in the control of hippocampal excitability, the role of serotonin (5-HT) and its receptors in normal and pathologic conditions, such as temporal lobe epilepsy (TLE), is still unclear. The present study was therefore designed firstly to investigate the acute effect of 8-OH-DPAT, a mixed 5-HT 1A/7 receptor agonist, at a high dose (1 mg/kg, i.p.) known to have antiepileptic properties, in a model of acute partial epilepsy in rats. For this purpose, a maximal dentate activation (MDA) protocol was used to measure electrographic seizure onset and duration. In addition, the effect of 8-OH-DPAT on in vivo dentate gyrus cell reactivity and short- and long-term plasticity was studied. Rats injected with 8-OH-DPAT exhibited a significant reduction in MDA and epileptic discharges, a decrease in paired-pulse facilitation and an increase in long-term potentiation. This study suggests that 8-OH-DPAT or in general 5-HT1A/7 agonists might be useful for the treatment of TLE and also have some beneficial effects on the comorbid cognitive disorders seen in epileptic patients.
AB - Although several studies have emphasized a crucial role for the serotonergic system in the control of hippocampal excitability, the role of serotonin (5-HT) and its receptors in normal and pathologic conditions, such as temporal lobe epilepsy (TLE), is still unclear. The present study was therefore designed firstly to investigate the acute effect of 8-OH-DPAT, a mixed 5-HT 1A/7 receptor agonist, at a high dose (1 mg/kg, i.p.) known to have antiepileptic properties, in a model of acute partial epilepsy in rats. For this purpose, a maximal dentate activation (MDA) protocol was used to measure electrographic seizure onset and duration. In addition, the effect of 8-OH-DPAT on in vivo dentate gyrus cell reactivity and short- and long-term plasticity was studied. Rats injected with 8-OH-DPAT exhibited a significant reduction in MDA and epileptic discharges, a decrease in paired-pulse facilitation and an increase in long-term potentiation. This study suggests that 8-OH-DPAT or in general 5-HT1A/7 agonists might be useful for the treatment of TLE and also have some beneficial effects on the comorbid cognitive disorders seen in epileptic patients.
KW - Dentate gyrus
KW - Depression
KW - Memory
KW - Serotonergic drugs
KW - Serotonin receptors
KW - Temporal lobe epilepsy
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U2 - 10.1007/s00221-013-3594-1
DO - 10.1007/s00221-013-3594-1
M3 - Article
C2 - 23780309
AN - SCOPUS:84885652304
SN - 0014-4819
VL - 230
SP - 441
EP - 451
JO - Experimental Brain Research
JF - Experimental Brain Research
IS - 4
ER -