Pharmaco-EEG-Based Classification of Psychotropic Activity of a Novel Chromone-Containing Allylmorpholine in Rats.

Abstract

Purpose: Chromone-containing allylmorpholines (CCAMs) are a promising class of compounds that have been shown to have a dose-dependent inhibition effect on locomotion in zebrafish (Danio rerio). However, experiments using behavioural tests on mice have not yet allowed us to fully understand the specificity of their action. In this study, we conducted a pharmacoencephalographic evaluation of the psychotropic effects of CCAM 33a on rats using a Naïve Bayes classifier (NBC) combined with the principal component analysis (PCA).

Methods: The ECoG experiments were conducted on white outbred rats. The training set, which was used as a reference for determining the pharmacological effects of each dose of the compound under study, included matrices of effects from 9 agents with different mechanisms of action. Amplitude-spectral analysis using PCA resulted in 6 new principal components that accounted for 83.57% of the variance. Classification of the effects of compound 33a was performed using NBC. To validate the classification results, additional experiments were conducted including the 5-hydroxytryptophan (5-HTP)-induced head twitch test and apomorphine-induced climbing in mice, as well as the 'presynaptic' low-dose apomorphine-induced yawning test in rats.

Results: CCAM 33a at doses of 100 and 300 mg/kg shows similar effects to hydroxyzine and sulpiride. In mouse experiments, CCAM 33a reduced the number of head twitches induced by 5-HTP administration at a dose of 20 mg/kg, and inhibited apomorphine-induced climbing at a dose of 300 mg/kg. In rats, the substance at a dose of 100 mg/kg reduced the number of yawns caused by apomorphine administration at a dose of 0.032 mg/kg.

Conclusion: The data obtained confirm the effectiveness of the combined use of NBC and PCA for classification tasks. The effects of the different doses of compound 33a on ECoG, as well as the abolition of the effects of apomorphine and 5-HTP in mice and rats, suggest a dopamine- and 5-HT2-blocking action of the molecule under study.