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-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.
authors.affiliation: Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Sezione di Fisiologia Umana, "G. Pagano", Università degli Studi di Palermo, Palermo, Italy, gergely.orban@unipa.it.
authors.forename: Gergely
authors.initials: G
authors.lastname: Orban
authors.forename: Massimo
authors.initials: M
authors.lastname: Pierucci
authors.forename: Arcangelo
authors.initials: A
authors.lastname: Benigno
authors.forename: Mauro
authors.initials: M
authors.lastname: Pessia
authors.forename: Salvatore
authors.initials: S
authors.lastname: Galati
authors.forename: Mario
authors.initials: M
authors.lastname: Valentino
authors.forename: Richard
authors.initials: R
authors.lastname: Muscat
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Giovanni
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: D017366:Serotonin Receptor Agonists; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin