Aminophylline and kindled seizures

The effects of aminophylline on amygdaloid and cortically kindled rats was studied. Rats implanted with chronic amygdaloid electrodes received either saline or 150 mg/kg, i.p., aminophylline 20 min prior to their first stimulation. On the first stimulation, aminophylline-treated rats had dramatically longer afterdischarge durations and more severe seizure ranks. When fully kindled, the animals were retested with saline or aminophylline. Again, the aminophylline-treated animals had longer afterdischarge durations than the saline-treated rats. In a second experiment, fully amygdaloid kindled rats were pretreated with various doses of aminophylline and stimulated 20 min later. With suprathreshold stimulation, a dose-dependent increase was noted in the afterdischarge duration. During seizure threshold determinations, aminophylline pretreatment markedly prolonged afterdischarge durations without significantly changing seizure severity or threshold. When animals were treated with the adenosine agonist, 2-chloroadenosine, prior to kindled amygdaloid stimulation, the elicited afterdischarge was shortened. The effect was antagonized where treatment with both 2-chloroadenosine and aminophylline occurred prior to amygdaloid stimulation. Rats with neocortical electrodes were also exposed to various doses of aminophylline while in a stable, partially developed kindled stage and again when fully kindled. At both stages, afterdischarge duration was increased by aminophylline in a dose-dependent manner. The partially developed, cortically kindled animals were more responsive to aminophylline than were those fully kindled and they tended to have greater increases in afterdischarge duration and seizure rank. These data demonstrate that aminophylline acts to prolong afterdischarges elicited at various stages of kindling from both amygdaloid and cortical sites.