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

ABSTRACT

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. 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. Low concentrations of E139 [/= 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 alpha2-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 alpha1-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%]. E139 suppressed population responses and in vitro epileptiform activity by both adrenergic and non-adrenergic mechanisms