Antagonism by Tetrabenazine of the Depressive Effects of Morphine on the Central Nervous System

Abstract

The authors have reported in the previous papers that tetrabenazine antagonizes morphine analgesia in mice (1) and that it has depressive effects on some afferent pathways in the central nervous system in rabbits and cats, like those of morphine (2). The questions arise whether the antagonistic effect by tetrabenazine of the central effects of morphine can be recognized in other species besides mice, whether all of the depressive actions of morphine on the afferent pathways of the central nervous system are suppressed by the tetrabenazine pretreatment, and whether tetrabenazine may owe its antagonistic action against morphine to its ability to deplete the catecholamines and serotonin levels in the brain.The purpose of this study was to investigate these questions using the electro physiological techniques. METHODSA total of 48 male albino rabbits weighing from 2.5 to 3.0 kg were employed in the EEG experiments and 15 adult male cats weighing from 2.5 to 3.0 kg were used for the experiments of evoked potentials.The methods of both experiments were exactly similar to those described in the previous paper (2). The drugs used in the present experiments were tetrabenazine met hanesulphonate, morphine hydrochloride and dl-3,4-dihydroxyphenylalanine (DOPA), all of which were administered by the intravenous route. RESULTS1. The spontaneous EEG of unanesthetized and non-curarized rabbits restrained stereotaxicallyThe spontaneous EEG of unanesthetized rabbits restrained stereotaxically was classified into three patterns which were fully described in the previous paper (2). The outline of these patterns are as follows :