Racine R, Coscina D V
Brain Res Bull. 1979 Jan-Feb;4(1):1-7. doi: 10.1016/0361-9230(79)90050-9.
Previous research has suggested that brain serotonin (5-hydroxytryptamine or 5-HT) neurons inhibit epileptiform seizure activity. To test further this possibility, experiments were performed to determine if brain 5-HT depletion would enhance the occurrence and/or magnitude of seizures "kindled" from the amygdala or neocortex of rats. Two modes of 5-HT depletion were used: (1) radiofrequency heat lesions of the midbrain dorsal and median raphe nuclei, and (2) systemic injection of the 5-HT synthesis inhibitor, p-chlorophenylalanine (pCPA). Both modes of 5-HT depletion reliably enhanced the strength of motor convulsions kindled from the cortex. Systemic pCPA also reduced the duration of after-discharges (ADs) in cortically-stimulated rats. However, pCPA reduced rather than enhanced convulsions kindled from the amygdala. In contrast to this, raphe lesions appeared to sensitize rats to the effects of amygdaloid kindling, i.e., lesions lowered AD thresholds, AD durations and number of ADs to elicit motor convulsions. Viewed together, these data support the hypothesis that 5-HT neurons can serve to inhibit seizures. However, the lack of robustness across parameters of epileptogenesis as well as discrepant findings related to 5-HT depletion mode additionally suggest that kindled seizures affect other neuronal populations in addition to those under serotonergic influence.
先前的研究表明，脑内血清素（5-羟色胺或5-HT）神经元可抑制癫痫样发作活动。为了进一步验证这种可能性，进行了实验以确定脑内5-HT耗竭是否会增加大鼠杏仁核或新皮质“点燃”的癫痫发作的发生率和/或强度。采用了两种5-HT耗竭模式：（1）中脑背侧和中缝核的射频热损伤，以及（2）全身注射5-HT合成抑制剂对氯苯丙氨酸（pCPA）。两种5-HT耗竭模式均可靠地增强了皮质点燃的运动性惊厥的强度。全身注射pCPA还缩短了皮质刺激大鼠的放电后持续时间（ADs）。然而，pCPA降低而非增强了杏仁核点燃的惊厥。与此相反，中缝核损伤似乎使大鼠对杏仁核点燃的效应敏感，即损伤降低了引发运动性惊厥的AD阈值、AD持续时间和AD次数。综合来看，这些数据支持5-HT神经元可抑制癫痫发作的假说。然而，癫痫发生各参数缺乏稳定性以及与5-HT耗竭模式相关的矛盾结果还表明，点燃的癫痫发作除了影响受5-羟色胺能影响的神经元群体外，还影响其他神经元群体。
