Effect of aminophylline on amygdaloid-kindled postictal inhibition.
Previous studies have shown that methylxanthines such as aminophylline increase the clinical severity and length of electrically elicited limbic afterdischarges in naive and kindled rats without lowering seizure threshold. When fully amygdaloid-kindled rats are electrically stimulated at intertrial stimulation intervals of less than 60 minutes, significant residual inhibition can be demonstrated. The present study examines the effect of three doses of aminophylline (25, 50 and 100 mg/kg) on repeated daily stimulations of fully amygdaloid-kindled rats. After 100 mg/kg aminophylline, the first elicited amygdaloid-kindled seizure afterdischarge was doubled in length compared to saline controls. The second elicited seizure 15 minutes later resulted in status epilepticus and hindlimb extension in the majority of the aminophylline-treated animals with death occurring in 28%. When 25 or 50 mg/kg of aminophylline was given daily for five days before the first of five daily stimulation trials, each separated by 15 minutes, no significant reduction in postictal inhibition was demonstrated compared to saline controls. The 50 mg/kg aminophylline dose consistently and significantly lengthened only the first afterdischarge of each day without affecting the postictal inhibition seen with repeated stimulations. The neural substrate that governs immediate postictal inhibition of amygdaloid-kindled seizures appears to be resistant to modification by aminophylline at low doses. At high doses of aminophylline (100 mg/kg), sustained epileptical activity occurred. The sustained seizure activity seen at the high dose of aminophylline may be secondary to blockade of the processes which normally terminate seizure activity, or it may represent actual inhibition of the immediate postictal inhibitory processes.
D000241:Adenosine / Q000502:physiology; D000628:Aminophylline / Q000494:pharmacology*; D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000628:Aminophylline; D000241:Adenosine