Terzioğlu Berna, Aypak Cenk, Onat Filiz Y, Küçükibrahimoğlu Esra, Ozkaynakçi Aydan E, Gören M Zafer
Department of Pharmacology and Clinical Pharmacology, Marmara University School of Medicine, 81326 Haydarpaşa, Istanbul, Turkey.
J Pharmacol Sci. 2006 Mar;100(3):227-33. doi: 10.1254/jphs.fp0050691. Epub 2006 Mar 14.
Genetic absence epilepsy rats from Strasbourg (GAERS), a selectively inbred strain of Wistar rats, has been validated as an experimental model for human absence epilepsy. In this model, systemic administration of ethosuximide (ETX) was shown to reduce the spike and wave discharges (SWD). In this study, gamma-aminobutyric acid (GABA) and L-glutamic acid levels in response to ETX injections (i.p., 100 mg/kg) were measured in the microdialysis samples collected from the ventrolateral thalamus (VLT) and the primary motor cortex (M1) area of Wistar rats and GAERS by using HPLC with fluorescent detection. Throughout the microdialysis procedure, continuous EEG recording was performed where ETX was shown to suppress the SWD activity. We demonstrated increased basal GABA levels in the M1 and VLT of GAERS, and ETX treatment did not produce any effect on higher GABA levels in the VLT, but suppressed the increased GABA levels significantly in the M1 of GAERS. All these findings denote the importance of corticothalamic circuitry and the role of increased GABA tonus in primary motor cortex and thalamus of GAERS. The primary motor cortex also seems to be involved in the SWD activity and ETX exerts, at least partially, its neurotransmitter effects through it.
来自斯特拉斯堡的遗传性失神癫痫大鼠（GAERS）是一种经过选择性培育的Wistar大鼠品系，已被确认为人类失神癫痫的实验模型。在该模型中，已证明全身给予乙琥胺（ETX）可减少棘波和慢波放电（SWD）。在本研究中，通过使用带荧光检测的高效液相色谱法，对从Wistar大鼠和GAERS的腹外侧丘脑（VLT）和初级运动皮层（M1）区域采集的微透析样本中，对ETX注射（腹腔注射，100 mg/kg）的反应中γ-氨基丁酸（GABA）和L-谷氨酸水平进行了测量。在整个微透析过程中，进行了连续脑电图记录，结果显示ETX可抑制SWD活动。我们证明GAERS的M1和VLT中基础GABA水平升高，ETX治疗对VLT中较高的GABA水平没有任何影响，但显著抑制了GAERS的M1中升高的GABA水平。所有这些发现表明皮质丘脑回路的重要性以及GAERS初级运动皮层和丘脑中GABA张力增加的作用。初级运动皮层似乎也参与了SWD活动，并且ETX至少部分地通过它发挥其神经递质作用。
