High dose of 8-OH-DPAT decreases maximal dentate gyrus activation and facilitates granular cell plasticity in vivo

Gergely Orban; Massimo Pierucci; Arcangelo Benigno; Mauro Pessia; Salvatore Galati; Mario Valentino; Richard Muscat; Giuseppe Di Giovanni

doi:10.1007/s00221-013-3594-1

High dose of 8-OH-DPAT decreases maximal dentate gyrus activation and facilitates granular cell plasticity in vivo

Gergely Orban
, Massimo Pierucci
, Arcangelo Benigno
, Mauro Pessia
, Salvatore Galati
, Mario Valentino
, Richard Muscat
, Giuseppe Di Giovanni

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

Abstract

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-HT_1A/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.

Original language	English
Pages (from-to)	441-451
Number of pages	11
Journal	Experimental Brain Research
Volume	230
Issue number	4
DOIs	https://doi.org/10.1007/s00221-013-3594-1
Publication status	Published - Oct 2013
Externally published	Yes

Keywords

Dentate gyrus
Depression
Memory
Serotonergic drugs
Serotonin receptors
Temporal lobe epilepsy

ASJC Scopus subject areas

General Neuroscience

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10.1007/s00221-013-3594-1

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title = "High dose of 8-OH-DPAT decreases maximal dentate gyrus activation and facilitates granular cell plasticity in vivo",

abstract = "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.",

keywords = "Dentate gyrus, Depression, Memory, Serotonergic drugs, Serotonin receptors, Temporal lobe epilepsy",

author = "Gergely Orban and Massimo Pierucci and Arcangelo Benigno and Mauro Pessia and Salvatore Galati and Mario Valentino and Richard Muscat and \{Di Giovanni\}, Giuseppe",

note = "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.",

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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

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KW - Depression

KW - Memory

KW - Serotonergic drugs

KW - Serotonin receptors

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High dose of 8-OH-DPAT decreases maximal dentate gyrus activation and facilitates granular cell plasticity in vivo

Abstract

Keywords

ASJC Scopus subject areas

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