Increased effectiveness of tacrine by deprenyl co-treatment in rats: EEG and behavioral evidence.
The acetylcholinesterase inhibitor tacrine and the monoamine oxidase inhibitor deprenyl are considered useful pharmacotherapies for Alzheimer's disease (AD). We assessed whether co-administration of these two compounds increases their effectiveness against two measures of cholinergic-monoaminergic hypofunction in rats, cortical EEG slowing and impaired spatial performance. EEG slowing induced by cholinergic-monoaminergic blockade was reversed by both deprenyl (10 - 50 mg/kg) and tacrine (1 - 20 mg/kg), but co-treatment with a subthreshold dose of deprenyl plus tacrine was markedly more effective. Neither tacrine (5 mg/kg) nor deprenyl (10 mg/kg) alone reduced water maze deficits due to cholinergic-monoaminergic hypofunction, but co-treatment (using these doses) improved performance. Cholinergic-monoaminergic co-treatment may constitute a useful pharmacotherapy to correct physiological and behavioral dysfunction due to neurotransmitter deficiencies in AD.
Dringenberg
H C
HC
Department of Psychology, Queen's University, Kingston, Ontario, Canada.
Laporte
P P
PP
Diavolitsis
P
P
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004357:Drug Synergism; D004569:Electroencephalography / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D012110:Reserpine / Q000494:pharmacology; D012601:Scopolamine / Q000494:pharmacology; D012642:Selegiline / Q000494:pharmacology*; D013619:Tacrine / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D013619:Tacrine; D012110:Reserpine; D012601:Scopolamine