Previous experiments have shown that tianeptine, a new psychotropic agent with antidepressant properties, improves performance in several learning and memory tasks in mice. In more recent investigations, tianeptine was found to completely alleviate working memory deficits produced by long-term alcohol intoxication and to prevent abnormal memory loss in aged animals (Jaffard et al, 1991b, 1991c). The aim of this paper was to examine how this last finding may be integrated in our understanding of brain mechanisms involved in memory loss. For this purpose, we present a brief review of experimental data and theories which, at different levels of analysis, seems to be relevant to this issue. Together with the subsequent examination of the conditions in which tianeptine was found to improve long-term retention, we suggest that: i) long-term memory loss would be largely determined by the initial encoding of information, so that ii) tianeptine would help aged animals to use spatial mapping or configural associations more efficiently at the time of initial acquisition. This, in turn, suggests that one of the main brain target sites for tianeptine in enhancing memory is the hippocampal formation.