Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Sezione di Fisiologia Umana, "G. Pagano", Università degli Studi di Palermo, Palermo, Italy,
Exp Brain Res. 2013 Oct;230(4):441-51. doi: 10.1007/s00221-013-3594-1. Epub 2013 Jun 19.
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.
尽管有几项研究强调了 5-羟色胺能系统在控制海马兴奋性中的关键作用，但 5-羟色胺（5-HT）及其受体在正常和病理条件下（如颞叶癫痫（TLE））的作用仍不清楚。因此，本研究首先旨在研究高剂量（1mg/kg，ip）8-OH-DPAT（一种混合 5-HT1A/7 受体激动剂）在大鼠急性部分癫痫模型中的急性作用。为此，使用最大齿状回激活（MDA）方案来测量电发作的起始和持续时间。此外，还研究了 8-OH-DPAT 对体内齿状回细胞反应性以及短期和长期可塑性的影响。注射 8-OH-DPAT 的大鼠 MDA 和癫痫放电明显减少，成对脉冲易化减少，长时程增强增加。这项研究表明，8-OH-DPAT 或一般 5-HT1A/7 激动剂可能对 TLE 的治疗有用，并且对癫痫患者中常见的共患认知障碍也有一些有益的影响。
