Amineptine is a tricyclic antidepressant agent with a unique capacity to reduce dopamine uptake selectively in vitro: this effect is also obtained in vivo. In vivo, amineptine increases striatal homovanillic acid without affecting the levels of other metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxytyramine. However, relatively high doses of amineptine preferentially lower the extracellular DOPAC level, assessed by pulse voltammetry, in the nucleus accumbens but not in the striatum. Microdialysis techniques confirm an increase in extracellular dopamine in various brain areas (striatum, nucleus accumbens and frontal cortex) and an increase in extracellular noradrenaline in the frontal cortex and dorsal hippocampus. Chronic treatment with amineptine induces downregulation of dopamine D2, beta- and alpha 2-adrenergic receptors. Amineptine enters the brain and its pharmacological effects are probably induced by the unchanged drug, rather than its two main metabolites.