Norepinephrine and E139 interactions on epileptiform activity in the rat hippocampus in vitro.

Objectives: We tested if E139, an anticonvulsant enaminone, interacts with norepinephrine (NE) to suppress population responses and chemically induced in vitro seizures in the rat hippocampus.

Materials And Methods: Evoked field population spikes (PS) were recorded in the hippocampal CA1 area, and in vitro seizures were generated chemically using the zero Mg(2+) model.

Results: Low concentrations of E139 (or=100 microM) enhanced them. For example, E139 (10 microM) depressed the PS amplitude by -23.9 +/- 2.3%, while 1 mM caused an enhancement. NE also depressed the PS by -34.5 +/- 6.0% and prevented E139 from subsequently depressing the PS amplitude. UK 14304, a selective alpha(2)-adrenoceptor agonist, also depressed the PS amplitude by -32.6 +/- 9.4% and occluded E139 suppression. NE suppression of PS was blocked by phentolamine and yohimbine which also blocked the effect of E139. Prazosin, a selective alpha(1)-adrenoceptor antagonist, did not block NE (-24.8 +/- 6.9%) or E139 (-29.7 +/- 6.1%) effects. Zero Mg(2+) buffer transformed a single PS to multiple spikes (MS; 3-8 spikes) and also induced spontaneous bursts (SB; 5-20/min). NE suppressed the number of MS from 5.6 +/- 0.3 to 3.8 +/- 0.2. At its peak effect, E139 was able to further suppress the number of MS to 3.0 +/- 0.3. Yohimbine did not change the number of MS but blocked the NE- and E139-induced suppression of MS. SB frequency was suppressed by NE (-60.8 +/- 11.7%) which occluded E139 effects. Finally, SB were reversibly abolished by yohimbine (-94.5 +/- 11.7%).

Conclusion: E139 suppressed population responses and in vitro epileptiform activity by both adrenergic and non-adrenergic mechanisms.