Effect of tacrine on EEG slowing in the rat: enhancement by concurrent monoamine therapy.
A dominant electrophysiological characteristic of Alzheimer's disease (AD) is the loss of desynchronized EEG activity and shift toward low-frequency EEG synchronization. In rats, similar EEG changes resulted from administering the anti-cholinergic scopolamine (1 mg/kg) and the monoamine depletor reserpine (10 mg/kg); amplitude increases between 0.5-20 Hz, with the delta (0.5-4 Hz) and theta (4-8 Hz) bands affected most severely. The acetylcholinesterase inhibitor tacrine, at doses between 10 and 20 mg/kg, reversed these EEG changes; co-administration of tacrine and the noradrenaline-serotonin reuptake inhibitor imipramine (10 mg/kg) enhanced tacrine's action to suppress delta activity. Co-administration of tacrine and the monoamine-oxidase inhibitor pargyline (20 mg/kg) enhanced EEG restoration by tacrine in all frequency bands between 0.5 to 20 Hz, but co-administration of the selective serotonin reuptake inhibitor fluoxetine (2 mg/kg) was ineffective. These results show that some drug therapies aimed at concurrently stimulating cholinergic and monoaminergic neurotransmission are more effective in reversing EEG slowing than cholinergic therapy alone. Significant monoaminergic deficits occur in Alzheimer's disease, in addition to the atrophy of cholinergic neurons. Thus, combined cholinergic-monoaminergic therapy may provide an enhanced restoration of cortical functioning, in addition to limiting the required treatment dose of cholinesterase inhibitors.
Dringenberg
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HC
Department of Psychology, Queen's University, Kingston, Ontario, Canada. dringenb@psyc.queensu.ca
Diavolitsis
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P
Noseworthy
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PA
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004569:Electroencephalography / Q000187:drug effects*; D005473:Fluoxetine / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D012110:Reserpine / Q000494:pharmacology; D012601:Scopolamine / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013619:Tacrine / Q000494:pharmacology*
D018759:Adrenergic Uptake Inhibitors; D015306:Biogenic Monoamines; D002800:Cholinesterase Inhibitors; D005473:Fluoxetine; D007099:Imipramine; D008996:Monoamine Oxidase Inhibitors; D018727:Muscarinic Antagonists; D010293:Pargyline; D012110:Reserpine; D012601:Scopolamine; D017367:Selective Serotonin Reuptake Inhibitors; D013619:Tacrine