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 E EG synchronization. In rats, similar EEG changes resulted from administerin g the anti-cholinergic scopolamine(2 mg/kg) and the monoamine depletor rese rpine (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 acetylcholines terase inhibitor tacrine, at doses between 10 and 20 mg/kg, reversed these EEG changes; co-administration of tacrine and the noradrenaline-serotonin r euptake inhibitor imipramine (10 mg/kg) enhanced tacrine's action to suppre ss delta activity. Go-administration of tacrine and the monoamine-oxidase i nhibitor pargyline (20 mg/kg) enhanced EEG restoration by tacrine in all fr equency bands between 0.5 to 20 Hz, but co-administration of the selective serotonin reuptake inhibitor fluoxetine (2 mg/kg) was ineffective. These re sults show that some drug therapies aimed at concurrently stimulating choli nergic and monoaminergic neurotransmission are more effective in reversing EEG slowing than cholinergic therapy alone. Significant monoaminergic defic its occur in Alzheimer's disease, in addition to the atrophy of cholinergic neurons. Thus, combined cholinergic-monoaminergic therapy may provide an e nhanced restoration of cortical functioning, in addition to limiting the re quired treatment dose of cholinesterase inhibitors. (C) 2000 Elsevier Scien ce Inc. All rights reserved.