Central effects following repeated treatment with antidepressant drugs

The review sums up the results of experiments in which there were studied central effects following repeated administration of various antidepressant drugs (AD) in rats and mice. A number of typical and atypical AD, except for selective inhibitors of 5-hydroxytryptamine (5-HT) uptake, potentiate the clonidine aggressiveness in mice (medicated by alpha 1-adrenoceptors). These results indicate that the repeated AD administration enhances responsiveness of central postsynaptic alpha 1-adrenoceptors. This assumption is in accordance with electrophysiological literature data. A few AD (including citalopram, a selective inhibitor of the 5-HT uptake), administered repeatedly, potentiate the locomotor hyperactivity induced by D-amphetamine or apomorphine, without affecting the stereotypy evoked by both dopaminomimetics. It may be supposed that AD enhance the responsiveness of a dopamine (DA) system, probably the mesolimbic one (but not the striatal one). A repeated administration of various AD also counteracts the locomotor hypoactivity induced by salbutamol (mediated by a beta-adrenoceptor). The importance of the effects stated above (alpha 1 up-regulation, DA up-regulation, beta down-regulation) for the mechanism of antidepressant action has been discussed.