Dringenberg_2000_Neuroreport_11_3513

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.