Involvement of both α₁- and β-Adrenoceptors in the Antagonism of Tetrabenazine-induced Effects by Antidepressants

Abstract

Antagonism of tetrabenazine-induced depressant effects in rodents is a widely used model to screen for antidepressant drugs (Howard et al., 1981). Like reserpine, tetrabenazine acts by depleting catecholamines and serotonin from their presynaptic storage sites. In contrast to the irreversible action of reserpine, however, tetrabenazine blocks the storage mechanism reversibly and has a rapid onset of action. Experimental data indicate that catecholamines play a more important role than serotonin. Unlike reserpine, tetrabenazine blocks pre-synaptic and post-synaptic dopamine receptors (Reches et al., 1983). The observed signs in mice are most frequently ptosis and hypothermia. The involvement of β-adrenoceptors in the mechanism of action of tricyclic antidepressants has been suggested (Frances et al., 1983; Souto et al., 1979) and β-adrenoceptor blockade shown to prevent the antagonist action of imipramine in reserpine-induced hypothermia. The present study was designed to examine which neuromediators, and, in particular, which adrenoceptor component, are involved in the anti-tetrabenazine effect of the noradrenaline uptake inhibitors desipramine and midalcipran. This latter drug, which also inhibits serotonin uptake, is devoid of any acute post-synaptic effects (Moret et al., 1985; Stenger et al., 1987).