5-HT1B receptors: A novel target for lithium - Possible involvement in mood disorders

Lithium ion is widely used to treat depressive patients, often as an initia l helper for antidepressant drugs or as a mood stabilizer; however, the tox icity of the drug mises serious problems, because the toxic noses of lithiu m are quite close to the therapeutic ones. Thus, precise characterization o f the target(s) involved in the therapeutic activity of lithium is of impor tance. The present work, cn-wien out at molecular, cellular, and in vivo le vels, demonstrates that 5-HT1B receptor constitutes a molecular target for lithium. Several reasons suggest that this interaction is more likely relat ed to the therapeutic properties of lithium than to its undesirable effects . First, the observed biochemical and functional interaction occurs at conc entrations that precisely correspond to effective therapeutic doses of lith ium. Second 5-HT1B receptors are well characterized as controlling the acti vity of the serotonergic system, which is known to be involved in affective disorders and the mechanism of action of various antidepressants. These fi ndings represent progress in our knowledge of the mechanism of action of li thium that may facilitate clinical use of the ion and also open new directi ons in the research of antidepressant therapies. (C) 1999 American College of Neuropschopharmacology. Published by Elsevier Science Inc.