Suppression of penicillin-induced focal epileptiform activity by locus ceruleus stimulation: mediation by an alpha 1-adrenoceptor.
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.
D000818:Animals; D004558:Electric Stimulation; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism* / Q000628:therapy; D010134:Fenclonine / Q000494:pharmacology; D008125:Locus Coeruleus / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010406:Penicillins; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism
D010406:Penicillins; D011942:Receptors, Adrenergic, alpha; D012701:Serotonin; D012110:Reserpine; D010134:Fenclonine; D009638:Norepinephrine