Suppression of penicillin-induced epileptiform activity by noxious stimulation: mediation by 5-hydroxytryptamine

Noxious stimulation has a well known suppressant effect on epileptiform activity in both laboratory animals and man. To study this phenomenon in an animal model, focal epileptiform activity was induced in anaesthetized rats by applying penicillin from one barrel of a micropipette while recording intracortical electrical activity from another barrel. Penicillin produced either focal epileptiform activity or focal penicillin spikes, depending somewhat on the rate of penicillin release. Focal epileptiform activity was suppressed by noxious stimulation, both somatic and olfactory, whereas non-noxious stimulation was ineffective in this regard. Focal penicillin spikes were only rarely suppressed by noxious stimulation. Reserpine blocked the suppressant effect of noxious stimulation as did p-chlorophenylalanine, a more selective depletor of 5-hydroxytryptamine. L-5-Hydroxytryptophan, a 5-hydroxytryptamine precursor, restored the suppressant effect of noxious stimulation blocked by reserpine and p-chlorophenylalanine. These results suggest that the suppression of SW by noxious stimulation is mediated by 5-hydroxytryptamine. Data from experiments employing pharmacological antagonists suggest the suppression of spike and wave activity by noxious stimulation not to be mediated by activation of dopamine receptors, alpha 2 or beta adrenoceptors, or muscarinic cholinoceptors. Prazosin, a selective alpha 1 adrenoceptor antagonist, did block the suppressant effect of noxious stimulation but only at a very high dose (2.4 mumols/kg). This likely reflects a known analgesic action of prazosin or weak binding to the 5-HT receptor. Methysergide, a 5-hydroxytryptamine antagonist, failed to antagonize the suppressant effect of noxious stimulation, however, many inhibitory actions of 5-hydroxytryptamine are not blocked by methysergide. It is concluded that suppression of focal epileptiform activity by noxious stimulation is mediated, at least in part, by 5-hydroxytryptamine.