EFFECTS OF A CHRONIC LITHIUM TREATMENT ON CENTRAL DOPAMINE NEUROTRANSPORTERS

The objectives of this study were to characterize the effects of a chr onic lithium (Li+) treatment on dopamine (DA) uptake sites, as well as on the levels of mRNA encoding for these transporters, and to determi ne the eventual reversibility of the treatment. Quantitative autoradio graphy was carried out on sections from rat brain using 3 beta-(4-[I-1 25]iodophenyl)tropane-2 beta-carboxylic acid isopropyl ester ([I-125]R T1-121) to label DA transporters, and mRNA levels were measured by in situ hybridization. Following chronic Li+ treatment (28 days), the lab elling to DA transporters increased (60-90%) in all sections of the ro stral and caudal neostriatum, whereas no alteration was observed in th e other regions studied, namely the substantia nigra, the ventral tegm ental 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 m RNA encoding for DA transporters in the substantia nigra and the ventr al tegmental area; however, no alterations were observed following a c hronic Li+ treatment, and thus the hypothesis of an increased synthesi s is not supported. This could mean that the Li+ treatment modified th e affinity of DA transporters for the radioligand, possibly a conseque nce of conformational changes induced by the disruption of the nerve t erminal membrane environment; however, a modification in the number of transporters could not be ruled out. The results of this study furthe r support the hypothesis of the implication of central dopaminergic tr ansmission in the pathology and-treatment of affective disorders. (C) 1991 Elsevier Science Inc.