Suppression of Penicillin‐Induced Focal Epileptiform Activity by Locus Ceruleus Stimulation: Mediation by an α1‐Adrenoceptor

Abstract

Application of penicillin to the cerebral cortex of anesthetized rats by pressure ejection from a micropipette resulted in the appearance of focal epileptiform activity with low rates of penicillin release and focal penicillin spikes with higher rates. Electrical stimulation of the locus ceruleus (LC), a major norepinephrine-containing nucleus in the brainstem, or of its axons projecting to the forebrain, the dorsal noradrenergic bundle, suppressed penicillin-induced focal epileptiform activity but was less effective in suppressing focal penicillin spikes. Depletion of monoamines with reserpine blocked the suppressant effect of LC stimulation. Neither the selective depletion of 5-hydroxytryptamine with p-chlorophenylalanine nor administration of methysergide reduced the effectiveness of LC stimulation, suggesting that 5-hydroxytryptamine probably does not mediate the suppression. Pimozide partially antagonized the suppression of focal epileptiform activity induced by LC stimulation, which is consistent with antagonism of .alpha.-adrenoceptors but not dopamine receptors. .beta.-Receptor antagonists did not block the suppression of focal epileptiform activity by LC stimulation, suggesting that .beta.-receptors are not important in the observed suppression. Prazosin, a selective .alpha.1-antagonist, at low doses blocked the suppression of focal epileptiform activity by LC stimulation whereas yohimbine, an .alpha.2-antagonist enhanced the stimulation-induced suppression. Taken together, the data are consistent with LC and dorsal bundle stimulation releasing norepinephrine, which in turn suppresses focal epileptiform activity by an action mediated by an .alpha.1-adrenoceptor.