Fragoso-Veloz J, Massieu L, Alvarado R, Tapia R
Departamento de Neurociencias, Universidad Nacional Autónoma de México, D.F.
Eur J Pharmacol. 1990 Mar 27;178(3):275-84. doi: 10.1016/0014-2999(90)90106-g.
The behavioral and electrographic effects of 4-aminopyridine (4-AP) administered i.p. or microinjected into the hippocampal CA1 region (i.h.) were studied in rats. The modification of such effects by the systemic administration of the Ca2+ antagonist dihydropyridine, nifedipine, was also studied. 4-AP i.p. (5 mg/kg) induced generalized tonic convulsions in 74% of the animals and death in 13%. Convulsions were characterized by electrical discharges of relatively short duration in all structures studied (frontal cortex, amygdala, dorsal hippocampus and dorsal raphe). Limbic seizures and frequent wet-dog shakes were observed when 4-AP was administered i.h. (2-4 nmol) and this behavior was correlated with hippocampal discharges, which rapidly propagated to the other structures. Pretreatment with nifedipine (7.5-50 mg/kg s.c.) markedly potentiated the effects of 4-AP. The percentage of rats that died during generalized convulsion after i.p. 4-AP increased to 56-87% and the frequency of wet-dog shakes increased after i.h. microinjection of 4-AP. Moreover, nifedipine-treated rats showed long-lasting (greater than 60 min) continuous discharges in all structures studied (status epilepticus). These results are discussed in the light of the possible participation of Ca2+ channels in the convulsant effect of 4-AP and its potentiation by nifedipine.
研究了腹腔注射（i.p.）或微量注射到海马CA1区（i.h.）的4-氨基吡啶（4-AP）对大鼠行为和脑电图的影响。还研究了全身给予钙拮抗剂二氢吡啶硝苯地平对这些影响的改变。腹腔注射4-AP（5mg/kg）使74%的动物发生全身性强直性惊厥，13%死亡。惊厥的特征是在所研究的所有结构（额叶皮质、杏仁核、背侧海马和背侧中缝核）中出现持续时间相对较短的放电。当脑内注射4-AP（2-4nmol）时，观察到边缘性癫痫发作和频繁的湿狗样抖动，这种行为与海马放电相关，海马放电迅速传播到其他结构。硝苯地平（7.5-50mg/kg皮下注射）预处理显著增强了4-AP的作用。腹腔注射4-AP后全身惊厥期间死亡的大鼠百分比增加到56-87%，脑内微量注射4-AP后湿狗样抖动的频率增加。此外，硝苯地平处理的大鼠在所研究的所有结构中出现持续时间长（大于60分钟）的连续放电（癫痫持续状态）。根据钙通道可能参与4-AP的惊厥作用及其被硝苯地平增强的情况对这些结果进行了讨论。
