Dringenberg_2002_Neuropharmacol_42_154

Considerable evidence indicates that both cholinergic ACh and serotonergic 5-HT inputs to the neocortex play a direct role in maintaining the activated state of the electroencephalogram EEG Here we investigated frequency-specific EEG effects of the 5-HT re-uptake inhibitor fluoxetine 10 and 20mg/kg to restore EEG activation abolished by combined treatment with the monoamine depletor reserpine 10 mg/kg and the muscarinic antagonist scopolamine 1 mg/kg Fluoxetine alone was ineffective in reversing EEG slowing produced by reserpine-scopolamine administration However fluoxetine suppressed EEG synchronization in the alpha 8-12 Hz band when administered concurrently with the 5-HT(1A receptor antagonist WAY 100635 0.5 mg/kg Further fluoxetine with and without WAY 100635 markedly potentiated the effectiveness of the acetylcholinesterase AChE inhibitor tacrine 5 mg/kg to restore EEG activation between 4-30 Hz These data indicate that 5-HT uptake inhibition and concurrent 5-HT(1A receptor blockade produce a limited normalization of the cortical EEG after monoaminergic-cholinergic blockade However fluoxetine strongly potentiates the effectiveness of tacrine to restore EEG activation Inhibitors of AChE are used to delay cognitive decline and EEG slowing in patients with Alzheimer's disease We suggest that doses of AChE inhibitors required for these effects can be reduced by concurrent 5-HT stimulation