Topographic pharmaco‐EEG mapping of increasing doses of buspirone and its comparison with diazepam

Abstract

It has been argued that representative drugs of the main psychopharmacological classes induce similar pharmaco‐EEG changes within groups but different changes between groups. The aim of this double‐blind, cross‐over, placebocontrolled study was to evaluate the effects of single oral doses of buspirone (BUS) 5, 15 and 30 mg in 15 healthy young subjects of both sexes on topographic maps of quantiative pharmaco‐EEG, using diazepam (DZP) 10 mg as reference compound. Sixteen lead recordings of three‐minute vigilance‐controlled EEG (V‐EEG) and four‐minute resting EEG (R‐EEG) were assessed at 0, 1, 2, 4, 6 and 8 hours after drug intake. EOG activity (vertical and horizontal) was also recorded in order to minimize ocular artifacts before applying an automatic artifact rejection method. MANOVA/Hotelling T² maps (multivariate analysis) showed a highly significant differentiation of DZP from placebo from the 1 st until the 8th hour all over the brain. After BUS a clear dose‐response was observed with effects being greater and longer lasting with increasing doses, the highest showing a peak effect in the 2nd hour which lasted until the 4th hour, mostly in central regions. Maps of drug‐induced pharmaco‐EEG changes as compared to placebo‐induced alterations (univariate analysis) demonstrated typical ‘anxiolytic pharmaco‐EEG patterns’ after DZP, characterized by a decrease of total power, attenuation of alpha activity and augmentation of beta activity, as well as by an increase of the centroid and centroid deviation of the total activity. Furthermore, a decrease of the centroid of the combined delta‐theta activity and an increase of the centroid of alpha activity was seen. In contrast, BUS produced an increase of theta activity with an acceleration of the centroid of the combined delta‐theta activity, no modification of alpha activity but a slowing down of its centroid and a tendency to reduce beta activity. The centroid of the total activity was also decreased. Although both compounds have proven their ability to reduce anxiety in patients, their different neurophysiological profiles suggest different neurobiological mechanisms of action after acute administration.