No abstract

The aim of the study was to detect whether antidepressants cause specific EEG effects in rats. The results presented are based on quantitative evaluation of a series of 6-min vigilance-controlled EEG recordings in rats under standardized conditions. Standard conditions comprised: a vigilance control, a rigid test procedure in which drugs and rats are divided according to a Greek-Latin square, and the same electrode placement. Computer analyses are based on an analysis of variance for which the averaged power spectral values are used as input. The use of a moving window technique in this type of EEG studies is introduced in comparison to the well-known use of fixed frequency bands. A number of antidepressants have been tested and several common characteristics are found.

The effects of a number of psycho-active drugs on electrocorticographic activity (ECoG) of the rat have been studied. Frontoparietal ECoG was recorded during 6-min periods immediately before drug/vehicle administration and starting at 20 and 45 min after administration. For each 6-min recording time, a mean power spectrum was calculated and smoothed. A quotient of the power at 20 and 45 min after and before drug, respectively, was then calculated. These quotients were used as input for an analysis of variance, followed by a t test and a normalization for the degrees of freedom, resulting in so-called n-profiles. Although each drug has its own characteristic n-profile, n-profiles of drugs belonging to the same clinical class have some characteristics in common. An automated classification system of psychotropic drugs, based on parameters extracted from n-profiles by discriminant analysis, is presented. For the antidepressant drug class the success rate of correct classification of antidepressant drugs is between 53 and 88%, for a neuroleptic drug in the neuroleptic drug class the success rate is 87%, for an anxiolytic drug in the anxiolytic drug class 100% and for a psychostimulant drug in the psycho-stimulant drug class between 86 and 100%. For a reliable classification of a drug about 10 n-profiles of active doses are needed. Using n-profiles, it appeared also possible to discriminate between antidepressant, neuroleptic, anxiolytic and psychostimulant drugs based on visual judgement. Moreover, visual evaluation of the n-profiles enables 4 subclasses to be recognized within the antidepressant class, 2 subclasses within the neuroleptic and 2 subclasses within the anxiolytic class.

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.

Freely moving rats were implanted with cortical, caudal, thalamic, and reticular electrodes. Drugs were infused intravenously at a constant rate up to a final cumulative dose of 40, 50, or 60 mg/kg. Doses of 10 mg/kg imipramine, viloxazine, desmethylimipramine, mianserin, and maprotiline produced spike-wave complexes, spikes, and increased spindling. General sustained discharges occurred after 20 mg/kg of mianserin, viloxazine, imipramine, desmethylimipramine and amitriptyline, and after 30 mg/kg of maprotiline. An abnormal high-amplitude pattern was evident after mianserin, amitriptyline, imipramine, and desmethylimipramine. On the average, seizures were observed at 40 mg/kg and were seen after desmethylimipramine (50 mg/kg), mianserin (30 mg/kg), amitriptyline (20 mg/kg), imipramine (40 mg/kg), maprotiline (40 mg/kg), and zimelidine (50 mg/kg). Ranking the tested antidepressants in decreasing order in accordance with their relative (pro)convulsive properties gives:amitriptyline > mianserin >> imipramine > desmethylimipramine > viloxazine >> maprotiline >> zimelidine > clovoxamine > nomifensine = fluvoxamine.