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

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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-HT1A/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.

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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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Authors and Affiliations

  1. Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Sezione di Fisiologia Umana, “G. Pagano”, Università degli Studi di Palermo, Palermo, Italy

    Gergely Orban & Arcangelo Benigno

  2. Istituto Euro-Mediterraneo di Scienza e Tecnologia (IEMEST), Palermo, Palermo, Italy

    Gergely Orban, Massimo Pierucci, Mauro Pessia & Giuseppe Di Giovanni

  3. Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, Malta

    Massimo Pierucci, Mario Valentino, Richard Muscat & Giuseppe Di Giovanni

  4. Department of Internal Medicine, Section of Human Physiology, University of Perugia, Perugia, Italy

    Mauro Pessia

  5. Neurology Department, Neurocenter (EOC) of Southern Switzerland, Ospedale Civico, Lugano, Switzerland

    Salvatore Galati

  6. School of Biosciences, Cardiff University, Cardiff, UK

    Giuseppe Di Giovanni

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  1. Gergely Orban
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  2. Massimo Pierucci
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  3. Arcangelo Benigno
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  8. Giuseppe Di Giovanni
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Correspondence to Gergely Orban or Giuseppe Di Giovanni.

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Orban, G., Pierucci, M., Benigno, A. et al. High dose of 8-OH-DPAT decreases maximal dentate gyrus activation and facilitates granular cell plasticity in vivo. Exp Brain Res 230, 441–451 (2013). https://doi.org/10.1007/s00221-013-3594-1

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  • DOI: https://doi.org/10.1007/s00221-013-3594-1

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