Noradrenergic mechanisms in hippocampal kindling with rapidly recurring seizures

Rats were subjected to hippocampal kindling with short interstimulus intervals (5 min), so-called rapid kindling. Severe depletion of forebrain noradrenaline (NA) with intraventricular 6-hydroxydopamine or blockade of alpha 2 adrenergic receptors with idazoxan markedly reduced the number of stimulations needed to induce the first severe limbic seizure and increased the total number of such seizures during 40 stimulations. Intracerebral microdialysis demonstrated a 3-fold increase of extracellular NA levels in response to the first kindling stimulations in both the stimulated and the non-stimulated hippocampus. The NA levels then gradually tapered off reaching baseline levels after 14 stimulations. We conclude that central noradrenergic neurons exert a powerful suppressant action, most probably mediated via an alpha 2 adrenergic receptor, on seizure development in rapid hippocampal kindling.