Pharmacological effects of alcohol may help in understanding the consequence of the difference in the mechanism of action of antidepressants inhibiting the reuptake of monoamines (RUI) and tianeptine which increases serotonin reuptake. Alcohol, similarly as reserpine, increases serotonin release into the synaptic cleft followed by its fast enzymatic metabolization. A long-term high consumption of alcohol may cause chronic defi cit of serotonin and „pharmacogenic“ depression which is worsened by chronic stress induced by social and economic degradation of the alcoholic. RUI increase the concentration of serotonin in the synaptic cleft, but serotonin does not decrease the activation of the hypothalamo-pituitary-adrenal axis. Antidepressant effects of RUI can be explained by the events beyond the synaptic receptors, esp. by an amelioration of neuroplasticity and a correction of structural defi cits in hippocampus and other brain areas. Tianeptine does not increase the concentration of serotonin in the synaptic cleft and keeps it from enzymatic degradation. Tianeptine shields hippocampus from the noxious effects of stress on dendrites. On this level, its effects are comparable to the effects of RUI. Favourable therapeutic effects of some RUI in alcohol dependence are connected probably with the fi rst step of their action, i.e. increase of concentration of serotonin in the synaptic cleft which simulates the acute action of alcohol. The missing evidence of therapeutic effects of tianeptine in nondepressed alcoholics might be explained by the fact that it does not increase serotonin concentration in the synaptic cleft. On the other hand, the increase of serotonin reuptake by tianeptine might have an advantage over serotonin reuptake inhibition in the treatment of depression in patients dependent on alcohol, because it has a more direct protective effects from stress.

        Key words: alcohol, serotonin, depression, SSRI, tianeptine.