Effects of metrifonate on the hippocampal theta rhythm of freely moving intact and MS-lesioned mice.
Changes in hippocampal electroencephalogram (EEG) have been suggested to be closely associated with spatial learning ability. Spatial learning can be improved in medial septal (MS)-lesioned mice by metrifonate, a cholinesterase inhibitor. We designed this study to investigate the effects of metrifonate on the hippocampal theta oscillation of intact and MS-lesioned mice. Intact and MS-lesioned C57BL mice were treated with acute injections of metrifonate (doses: 15, 50 and 100 mg/kg ip). These included a dose that considerably improved spatial memory of MS-lesioned mice in our earlier study. In addition, subtype selective muscarinic agents, BIBN-99, AF267B and AF150(S) were used. Recordings of hippocampal theta during movement and awake immobility revealed a dramatic reduction of theta in the lesioned animals. Metrifonate induced prominent changes in the EEG of intact mice, but not of MS-lesioned mice. The effect of metrifonate was not mimicked by two selective M(1)-agonists and was augmented by a combined injection of a selective M(2)-antagonist. These data suggest that improved spatial learning by the cholinesterase inhibitor metrifonate is unrelated to its effects on the hippocampal EEG. These two effects may be mediated through different muscarinic receptor subtypes.
Ikonen
S
S
Department of Neuroscience and Neurology and the University Hospital, University of Kuopio, P.O. Box 1627, 70211, Kuopio, Finland.
Tanila
H
H
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018721:Muscarinic Agonists / Q000494:pharmacology; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000187:drug effects; D020665:Septum of Brain / Q000033:anatomy & histology / Q000502:physiology*; D013028:Space Perception / Q000187:drug effects; D013826:Theta Rhythm / Q000187:drug effects*; D014236:Trichlorfon / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D018721:Muscarinic Agonists; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D014236:Trichlorfon