Frequency- and structure-dependent inhibition of normal and epileptiform activity by 6-benzoyldeltamine in rat hippocampal slices

The present study investigated the effects of the Aconitum alkaloids 6-benz oyldeltamine and the structurally related eldeline on neuronal activity in rat hippocampal slices. 6-Benzoyldeltamine (1-30 mu M) decreased the orthod romic field potentials recorded in area CA1 in a concentration-dependent ma nner. The inhibitory effect of eldeline (3-100 mu M) was lower. The attenua tion of the postsynaptic population spike was accompanied by a simultaneous decrease in the presynaptic fibre spike evoked by electrical stimulation o f the Schaffer collaterals. The input-output relationship of the presynapti c fibre spike as function of the stimulation intensity, and for the postsyn aptic population spike as function of the presynaptic fibre spike was shift ed to the right. Thus, electrophysiologically, these alkaloids seem to inhi bit predominantly the excitability of the afferent fibres and, in consequen ce, neurotransmission between Schaffer collaterals and the CA1 neurons, the reby suppressing the firing of the latter. The inhibitory action of 6-benzo yldeltamine revealed use-dependence as obvious by an enhanced attenuation o f the antidromic spike when stimulation frequency was increased. 6-Benzoyld eltamine inhibited stimulus-triggered epileptiform population bursts in are a CA1 elicited by omission of Mg2+, as well as spontaneously occurring epil eptiform discharges in area CA3 elicited by omission of Mg2+ and elevation of K+. Complete suppression of spontaneous activity was observed at 1 mu M 6-benzoyldeltamine, which reduced the population spike only by about 20% of control. It is concluded that the inhibitory and antiepileptiform effect o f 6-benzoyldeltamine is mediated by a frequency-dependent decrease in excit ability, which might be important for filtering high frequency bursts of ac tion potentials characteristic for epileptiform activity in the hippocampus . (C) 1999 Elsevier Science B.V. All rights reserved.