Salgado-Commissariat D, Alkadhi K A
Department of Pharmacological and Pharmaceutical Sciences University of Houston, TX 77204-5515, USA.
Brain Res. 1996 Dec 16;743(1-2):212-6. doi: 10.1016/s0006-8993(96)01044-x.
The seizure susceptibility in genetically epilepsy prone rats (GEPRs) is reported to be caused by abnormalities in several neurotransmitter systems including the serotonergic system. Among the reported abnormalities is a decrease in brain serotonin content. Therefore, we examined the effects of exogenous serotonin on brain slices from the severe seizure strain of GEPRs (GEPR-9s). We employed conventional electrophysiological techniques to record from CA1 pyramidal neurons of hippocampi of GEPR-9s. The membrane resting potential and input resistance of the GEPR-9 CA1 pyramidal neurons were not different from those of the Sprague-Dawley rats. Serotonin (20 microM) inhibited the directly and synaptically evoked action potentials in GEPR-9 CA1 neurons, as it did in the Sprague Dawley neurons, but only in some and not all of the neurons tested (blocked the directly evoked potentials in 57% and synaptically evoked potentials in 33.3% of the total neurons). This inhibition was also accompanied by hyperpolarization and reduction of membrane input resistance. In the bicuculline-treated brain slices of the GEPR-9, serotonin inhibited the epileptiform bursts causing concurrent hyperpolarization and reduction in membrane input resistance. The effects of the selective serotonin 5-HT1A receptor agonist, 8-OH-DPAT (20 microM) on GEPR-9 pyramidal CA1 neurons were similar to those of serotonin, except the magnitude of hyperpolarization and reduction of membrane input resistance were less than those produced by serotonin. We conclude that the apparent decrease in sensitivity of the GEPR-9 CA1 pyramidal neurons to serotonin may represent a deficiency of serotonin 5-HT1A receptor.
据报道，遗传性癫痫易感大鼠（GEPRs）的癫痫易感性是由包括血清素能系统在内的几种神经递质系统异常引起的。报道的异常情况之一是脑血清素含量降低。因此，我们研究了外源性血清素对GEPRs严重癫痫发作品系（GEPR - 9s）脑片的影响。我们采用传统电生理技术记录GEPR - 9s海马CA1锥体神经元的电活动。GEPR - 9 CA1锥体神经元的膜静息电位和输入电阻与Sprague - Dawley大鼠的并无差异。血清素（20微摩尔）抑制GEPR - 9 CA1神经元的直接和突触诱发动作电位，就像在Sprague Dawley神经元中一样，但仅在部分而非全部测试神经元中出现（在总计神经元中，阻断直接诱发电位的占57%，阻断突触诱发电位的占33.3%）。这种抑制还伴随着超极化和膜输入电阻降低。在经荷包牡丹碱处理的GEPR - 9脑片中，血清素抑制癫痫样爆发，同时引起超极化和膜输入电阻降低。选择性血清素5 - HT1A受体激动剂8 - OH - DPAT（20微摩尔）对GEPR - 9锥体CA1神经元的作用与血清素相似，只是超极化幅度和膜输入电阻降低程度小于血清素所产生的效果。我们得出结论，GEPR - 9 CA1锥体神经元对血清素的敏感性明显降低可能代表血清素5 - HT1A受体缺乏。
