REGULATION OF CENTRAL SEROTONIN TRANSPORTERS BY CHRONIC LITHIUM - AN AUTORADIOGRAPHIC STUDY

The objectives of this study were to further characterize the effects of a chronic lithium (Li+) treatment on seratonin (5-HT) uptake sites, and to determine the eventual reversibility of the observed effects. Quantitative autoradiography experiments were carried out on sections from rat brain, using [H-3]citalopram to label selectively the 5-HT tr ansporters or uptake sites. In these experiments, we were able to satu rate the 5-HT transporters using an isotopic dilution of the radioliga nd. The lowest densities of [H-3]citalopram binding were measured in a ll cortical regions studied, with the highest cortical labelling in th e anterior cingulate cortex. The rostral neostriatum presented a moder ate density of labelling, with slightly higher levels in its ventral p ortion. Relatively high densities were measured in the globus pallidus , hippocampus, and hypothalamus. Finally, the highest densities were f ound in the brain stem. Indeed, the dorsal raphe nuclei as well as the substantia nigra were characterized by very high amounts of [H-3]cita lopram binding. The chronic administration of Li+ increased the densit y of 5-HT uptake sites in cortical regions, and significant difference s were observed in the frontal, temporal, and entorhinal-piriform cort ices, with an elevation, albeit not significant, in the anterior cingu late region. A significant increase was also observed in the lateral h ypothalamus. Since the 5-HT uptake sites were studied with saturating concentrations of citalopram, we can propose that this increase in bin ding densities can be attributed to an increase in the number of 5-HT transporters. Interestingly the only modifications observed were locat ed in regions containing nerve terminals of 5-HT neurons, while region s with cell bodies remained unaffected. Moreover, these effects were c ompletely reversed following a recovery of 48 h without Li+. Also, the re were no modifications in the density of 5-HT uptake sites after onl y 2 days of Li+. These results, suggesting an anatomically heterogenou s increase in 5-HT uptake in chronically treated rats, are in accord w ith clinical observations and previous reports with homogenate binding assays. Finally, the conclusions from this study further support the importance of central 5-HT synaptic transmission in the pathophysiolog y and treatment of human affective disorders. (C) 1997 Wiley-Liss, Inc .