The objectives of this study were to characterize the effects of a chronic lithium (Li+) treatment on dopamine (DA) uptake sites, as well as on the levels of mRNA encoding for these transporters, and to determine the eventual reversibility of the treatment. Quantitative autoradiography was carried out on sections from rat brain using 3beta-(4-[125I]iodophenyl)tropane-2beta-carboxylic acid isopropyl ester ([125I]RT1-121) to label DA transporters, and mRNA levels were measured by in situ hybridization. Following chronic Li+ treatment (28 days), the labelling to DA transporters increased (60-90%) in all sections of the rostral and caudal neostriatum, whereas no alteration was observed in the other regions studied, namely the substantia nigra, the ventral tegmental area, and the dorsal raphe nucleus. These effects were reversed completely following a withdrawal period of 2 days without Li+. Also, there were no modifications in the labelling of DA transporters after only 2 days of Li+ treatment. In addition, we measured the levels of mRNA encoding for DA transporters in the substantia nigra and the ventral tegmental area; however, no alterations were observed following a chronic Li+ treatment, and thus the hypothesis of an increased synthesis is not supported. This could mean that the Li+ treatment modified the affinity of DA transporters for the radioligand, possibly a consequence of conformational changes induced by the disruption of the nerve terminal membrane environment; however, a modification in the number of transporters could not be ruled out. The results of this study further support the hypothesis of the implication of central dopaminergic transmission in the pathology and treatment of affective disorders.