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Journal of the Korean Child Neurology Society 1997;5(2):207-216.
Published online May 30, 1997.
Modulatory Effects of Imipramine on Pilocarpine-induced Seizures in Immature Rats.
In Goo Lee, Young Hoon Kim, Kyung Tai Whang
Abstract
PURPOSE
Norepinephrine has modulatory effects on neuronal excitability and, in some cases, has a proconvulsant effect. Intraperitoneal imipramine treatment increases norepinephrine level, and to a lesser extent, dopamine and serotonin in brain dialysate from rats. We sought to determine the effects of imipramine on pilocarpine-induced seizures in the immature rats. METHODS: Right and left cortical and hippocampal electrodes were placed in 10~15 day old Sprague-Dawley rats. The following day 3-hour video EEG recordings were obtained to monitor electrographic seizures and status epilepticus induced by intraperitoneal injection of high dose(200mg/kg : HD) and low dose (75mg/kg : LD) pilocarpine. A first group of rats received HD pilocarpine alone(n=25), or pretreatment with 0.5(n=6). 1(n=6), 2(n=6), 5(n=6), or 10(n=11)mg/kg of imipramine. A second group of rats received LD pilocarpine alone(n=6) or pretreatment with 2mg/kg of imipramine (n=6). Data were analyzed using the Fisher exact test. RESULTS: Treatment with HD pilocarpine alone resulted in electrographic seizures in 76%(n=19) and status epilepticus in 44%(n=11). In the HD pilocarpine group, status epilepticus was seen in 100% of rats pretreated 1, 2, and 5mg/kg imipramine. 90.9% of the rats pretreated with 10mg/kg of imipramine developed seizures and 36.4% developed status epilepticus. Imipramine at 0.5, 1,2, and 5mg/kg increased the incidence of seizures and status epilepticus in the HD pilocarpine group, but the incidence was statistically significant only for status epilepticus(p<0.05). The latency for the occurrence of first status epilepticus was 12.3+/-1.3 min in the HD pilocarpine alone group, and it was 21+/-3.8 min and 25.3+/-5.7 min in the group pretreated with 5 and 10mg/kg imipramine, respectively(p<0.02). Treatment with LD pilocarpine alone resulted in seizures in 50% and status epilepticus in 16.7%. In the LD pilocarpine group with imipramine 2mg/kg pretreatment, 83.3% had seizures and status epilepticus. Imipramine at 2mg/kg increased the incidence of seizures and status epilepticus in the LD pilocarpine group, but the increase was statistically significant only for status epilepticus(p<0.05). CONCLUSION: Imipramine exhibits a proconvulsant effect at low doses and an anticonvulsant effect at high doses in the pilocarpine seizure model in immature rats. There may be a dose-dependent effect on monoaminergic receptors which results in increased neuronal excitability.
Key Words: Norepinephrine, Imipramine, Pilocarpine-induced seizure


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