Danober L, Depaulis A, Marescaux C, Vergnes M
Laboratoire de Neurophysiologie et Biologie des Comportements, Centre de Neurochimie du CNRS, Strasbourg, France.
Eur J Pharmacol. 1993 Apr 6;234(2-3):263-8. doi: 10.1016/0014-2999(93)90962-h.
Wistar rats of a selected strain show spontaneous generalized non-convulsive seizures with bilateral synchronous spike-wave discharges on the cortical electroencephalograph (EEG). The 7 to 9 c/s spike-wave discharges occur predominantly in waking states of inactivity. The effects of cholinergic drugs on the cumulated duration of spike-wave discharges were investigated in this rat model of absence epilepsy. I.p. injections of drugs which potentiate cholinergic neurotransmission, namely the acetylcholinesterase inhibitor, physostigmine (0.1-0.5 mg/kg), the muscarinic receptor agonists, oxotremorine (0.25-1 mg/kg) and pilocarpine (0.125-2 mg/kg), and the nicotinic receptor agonist, nicotine (0.062-2 mg/kg), suppressed discharges in a dose-dependent manner and induced an arousal-like cortical EEG. The muscarinic receptor antagonist, scopolamine, increased the spike-wave discharges at doses below 0.05 mg/kg; at higher doses (0.05-1 mg/kg) it decreased discharges and induced a sleep-like EEG. The nicotinic receptor antagonist, mecamylamine (0.5-6 mg/kg), had no effect on spike-wave discharges or the EEG. These results suggest that cholinergic activity accounts for the preferential occurrence of absence seizures in states of reduced arousal.
特定品系的Wistar大鼠会出现自发性全身性非惊厥性癫痫发作，在皮层脑电图（EEG）上有双侧同步棘波放电。7至9赫兹的棘波放电主要发生在清醒的不活动状态。在这种失神癫痫大鼠模型中，研究了胆碱能药物对棘波放电累积持续时间的影响。腹腔注射增强胆碱能神经传递的药物，即乙酰胆碱酯酶抑制剂毒扁豆碱（0.1 - 0.5毫克/千克）、毒蕈碱受体激动剂氧化震颤素（0.25 - 1毫克/千克）和毛果芸香碱（0.125 - 2毫克/千克）以及烟碱受体激动剂尼古丁（0.062 - 2毫克/千克），以剂量依赖性方式抑制放电，并诱发类似觉醒的皮层脑电图。毒蕈碱受体拮抗剂东莨菪碱在剂量低于0.05毫克/千克时增加棘波放电；在较高剂量（0.05 - 1毫克/千克）时减少放电并诱发类似睡眠的脑电图。烟碱受体拮抗剂美加明（0.5 - 6毫克/千克）对棘波放电或脑电图无影响。这些结果表明，胆碱能活动是失神发作在觉醒降低状态下优先发生的原因。
