AN INDIRECT CHOLINESTERASE INHIBITOR, METRIFONATE, INCREASES NEOCORTICAL EEG AROUSAL IN RATS

WE investigated the ability of a cholinesterase inhibitor, metrifonate , to desynchronize cortical EEG activity. Metrifonate suppressed immob ility-related high voltage spindling activity in young and aged rats a t doses of 30 and 60 kg(-1), p.o., and 10, 30 and 60 mg kg(-1), p.o., respectively. The increase in EEG 1-20 Hz amplitude induced by scopola mine (0.2 mg kg(-1), i.p.) was fully alleviated by metrifonate (30 and 100 mg kg(-1), p.o.) and partially alleviated by a reference cholines terase inhibitor, THA (3 and 6 mg kg(-1), i.p.). Nucleus basalis (NB) lesions induced by quisqualic acid decreased frontal cortical choline acetyltransferase activity by 80% and increased cortical EEG slow wave s. Metrifonate and THA did not reverse NE lesion-induced EEG abnormali ty. We conclude that metrifonate enhances cholinergic desynchronizatio n of cortical EEG waves and that a severe defect of presynaptic NE cho linergic fibres limits the therapeutic effects of metrifonate.