PHARMACO-EEG-BASED CLASSIFICATION OF PSYCHOTROPIC ACTIVITY OF A NOVEL CHROMONE-CONTAINING ALLYLMORPHOLINE IN RATS

Abstract

Purpose: Chromone-containing allylmorpholines (CCAMs) are a promising group for which a dose-dependent inhibition of locomotion in Danio rerio has been shown. Experiments using behavioural tests on mice did not allow to determine the specificity of the substance's action. In this study we performed a pharmacoencephalographic evaluation of the psychotropic activity of CCAM 33a in rats using Naïve Bayes classifier (NBC) combined with the Principal Component Analysis (PCA). Methods: The ECoG experiments were conducted in white outbred rats. The training set, used as a reference to determine the pharmacological effects of each dose of the studied compound, included matrixes of effects of 9 agents with different mechanisms of action. The amplitude-spectral analysis, by using PCA, resulted in 6 new principal components describing 83.57% of the variance. Classification of 33a effects was performed using NBC. To validate the classification results, additional experiments were performed including the 5-hydroxytryptophan (5-HTP)-induced head twitches test and apomorphine-induced climbing in mice, as well as the ‘presynaptic’ low-dose apomorphine-induced yawning test in rats. Results: CCAM 33a at a dose of 100 and 300 mg/kg demonstrates similar effects to those of hydroxyzine and sulpiride. In experiments in mice, CCAM 33a at a dose of 20 mg/kg reduced the number of head-twitches in mice induced by the administration of 5-HTP, and at a dose of 300 mg/kg inhibited apomorphine-induced climbing. In rats, the studied substance at a dose of 100 mg/kg reduced the number of yawns induced by the administration of apomorphine at a dose of 0.032 mg/kg. Conclusions: The obtained data confirm the effectiveness of combined use of NBC with PCA for classification tasks. The ECoG-effects of different doses of 33a, as well as the abolition of apomorphine and 5-HTP effects in mice and rats, suggest a dopamine- and 5-HT2-blocking action of the studied molecule.

Keywords: pharmaco-EEG, ECoG, rats, naive Bayes classifier, allylmorpholine derivatives, antipsychotic activity