PET study of 5-HT1A and GABA receptors in temporal lobe epilepsy.

已经证明，5-羟色胺通过激活CA 1锥体神经元中的5-HT 1A受体来抑制癫痫样放电。此外，已知5-HT 1A受体对大鼠杏仁核点燃发展的抑制作用。尽管癫痫可能涉及多巴胺能活动，但由于合适的配体有限，因此对癫痫中枢多巴胺能系统的研究很少。我们使用一种新的5-HT 1A受体放射性配体[11 C]WAY 100635，研究了颞叶癫痫患者和健康对照者的5-HT 1A受体。使用参考组织模型制作结合电位（BP）的参数图像，并使用SPM 99进行分析。我们发现，5-HT 1A受体结合在颞叶EEG病灶同侧显着减少。但在对侧颞叶也观察到结合减少。与使用[11 C]氟马西尼测量的GABA/苯二氮卓类受体相比，5-HT 1A结合面积减少更受限制。颞叶癫痫患者大脑皮层5-HT 1A结合减少可能反映了5-HT 1A受体抑制作用的降低。目前的研究结果表明，[11 C]WAY 100635的神经受体成像技术可能会为理解癫痫的病理生理学带来新的视角。

It has been demonstrated that serotonin inhibits epileptiform discharge by activation of 5-HT1A receptors in CA1 pyramidal neurons. Further, inhibitory role of 5-HT1A receptor for the development of amygdaloid kindling in rats has been known. In spite of possible involvements of serotoriergic activities, there have been few studies to investigate central serotonergic system in epilepsy, since suitable ligands have been limited. Using a new radioligand, [11C]WAY 100635 for 5-HT1A receptors, we investigated 5-HT1A receptors in patients with temporal lobe epilepsy and healthy controls. Parametric images of binding potential(BP) were made using the reference tissue model, and were analyzed using SPM99. We found marked decrease of 5-HT1A receptor binding in the temporal lobe ipsilateral to EEG foci. But decreased binding was also observed in the contra lateral temporal lobe. Decreased area of 5-HT1A binding was more restricted compared with that of GABA/benzodiazepine receptor which was measured using [11C]frumazenil. Deceresed 5-HT1A binding in the cortex may reflect decreased inhibitory role of 5-HT1A receptor in patients with temporal lobe epilepsy. The present findings suggest that neuroreceptor imaging techniques with [11C]WAY 100635 may give rise to new perspectives for understanding the pathophysiology of epilepsy.