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 immobility-related high voltage spindling activity in young and aged rats at doses of 30 and 60 mg 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 scopolamine (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 cholinesterase 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 waves. Metrifonate and THA did not reverse NB lesion-induced EEG abnormality. We conclude that metrifonate enhances cholinergic desynchronization of cortical EEG waves and that a severe defect of presynaptic NB cholinergic fibres limits the therapeutic effects of metrifonate.
Björklund
M
M
Department of Neurology, University of Kuopio, Finland.
Jäkälä
P
P
Schmidt
B
B
Riekkinen
M
M
Koivisto
E
E
Riekkinen
P
P
D000818:Animals; D001143:Arousal / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004569:Electroencephalography / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000494:pharmacology; D013377:Substantia Innominata / Q000201:enzymology / Q000254:growth & development / Q000502:physiology*; D014236:Trichlorfon / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D014236:Trichlorfon; D012601:Scopolamine