Mean power spectra from pharmaco-electrocorticographic studies: relative baseline correction and log transformation for a proper analysis of variance to assess drug effects.

The effects of drugs on electrocorticographic activity (ECoG) of the rat are studied in a routine screen. ECoG is recorded for 6-min periods before drug/vehicle administration and starting at 20 and 45 min thereafter. For each period, a mean power spectrum is calculated. Drugs are tested in 25 rats according to a 5 x 5 Latin square design and effects are assessed with analysis of variance. The validity of this assessment depends on assumptions on the chosen statistical model and the distribution of the data. In this study we consider the relative and absolute baseline corrected data. The assumptions appear to be better fulfilled if together with a relative baseline correction a logarithmic transformation is applied to the data.

Relationship between electrocortical activity and beta-adrenergic receptor function in the rat after chronic desimipramine treatment.

The aim of this study was to investigate the effects of chronic administration of desimipramine (DMI) after 2, 7 or 20 mg/kg per day, administered by osmotic minipumps, on electrocortical activity and beta-adrenergic receptors in rat brain. Rats receiving DMI chronically show a dose- and time-dependent increase of electrocortical activity above 15 Hz as well as a dose- and time-dependent decrease below 15 Hz. Already after 3 days of treatment a clear effect on the electrocorticogram (ECoG) was seen. The maximal change in the ECoG was reached at the end of the study, after 24 days of treatment. After acute treatment (20 and 45 minutes after 2, 4 or 10 mg/kg i.p.) with DMI, a decrease of electrocortical activity is seen above 15 Hz. Thus the effect of acute DMI treatment on the ECoG is different from that of chronic treatment. In the same group of rats the effect of chronic DMI treatment on the beta-adrenergic receptor number was determined 24 hours after the last ECoG recording. The number of beta-adrenergic receptors was dose dependently reduced in the DMI-treated rats as determined by [3H]-dihydroalprenolol binding. There was no change in affinity (KD) of the ligand for the beta-receptor. This finding was corroborated by a decrease in the functional activity of the beta-adrenergic receptors, as determined by isoprenaline stimulated efflux of cyclic-AMP in cortex slices. These data indicate that chronic treatment with DMI, resulting in a down-regulation of the cortical beta-adrenergic system, is paralleled by pronounced effects on the ECoG of rats. The different ECoG profiles after chronic DMI treatment compared with acute treatment suggest that adaptive changes in the electrical brain activity continually develop during the chronic treatment with this antidepressant drug.

Classification of psychotropic drugs by rat EEG analysis: the anxiolytic profile in comparison to the antidepressant and neuroleptic profile.

Electroencephalograms were recorded from the parietal and frontal cortex of freely moving rats held in constant vigilance by placing them in a slowly turning drum. The effects of 5 clinically effective anxiolytics, buspirone, meprobamate, phenobarbital, chlordiazepoxide and diazepam, were studied after intraperitoneal injection of different doses. After on-line fast Fourier transformation of the EEG signal, the drug effects were quantified by an Analysis of Variance. This resulted in a t profile for each drug dosage. Averaging the t profiles of all dosages of a drug results in a 'drug profile'. Averaging the drug profiles of the 5 anxiolytic drugs tested results in an 'anxiolytic profile'. This profile is characterized by a power decrease from 8 to 11 Hz and above 70 Hz and a power increase from 20 to 60 Hz. The anxiolytic profile is compared with the formerly defined antidepressant and neuroleptic profiles and can be clearly distinguished from the latter two.