TOPOGRAPHIC PHARMACO-EEG MAPPING OF INCREASING DOSES OF BUSPIRONE ANDITS COMPARISON WITH DIAZEPAM

It has been argued that representative drugs of the main psychopharmac ological classes induce similar pharmaco-EEG changes within groups but different changes between groups. The aim of this double-blind, cross -over, placebo-controlled study was to evaluate the effects of single oral doses of buspirone (BUS) 5, 15 and 30 mg in 15 healthy young subj ects of both sexes on topographic maps of quantitative pharmaco-EEG, u sing diazepam (DZP) 10 mg as reference compound. Sixteen lead recordin gs of three-minute vigilance-controlled EEG (V-EEG) and four-minute re sting EEG (R-EEG) were assessed at 0, 1, 2, 4, 6 and 8 hours after dru g intake. EOG activity (vertical and horizontal) was also recorded in order to minimize ocular artifacts before applying an automatic artifa ct rejection method. MANOVA/Hotelling T-2 maps (multivariate analysis) showed a highly significant differentiation of DZP from placebo from the Ist until the 8th hour all over the brain. After BUS a clear dose- response was observed with effects being greater and longer lasting wi th increasing doses, the highest showing a peak effect in the 2nd hour which lasted until the 4th hour, mostly in central regions. Maps of d rug-induced pharmaco-EEG changes as compared to placebo-induced altera tions (univariate analysis) demonstrated typical 'anxiolytic pharmaco- EEG patterns' after DZP, characterized by a decrease of total power, a ttenuation of alpha activity and augmentation of beta activity, as wel l as by an increase of the centroid and centroid deviation of the tota l activity. Furthermore, a decrease of the centroid of the combined de lta-theta activity and an increase of the centroid of alpha activity w as 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 a nd a tendency to reduce beta activity. The centroid of the total activ ity was also decreased. Although both compounds have proven their abil ity to reduce anxiety in patients, their different neurophysiological profiles suggest different neurobiological mechanisms of action after acute administration.