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 initial helper for antidepressant drugs or as a mood stabilizer; however, the toxicity of the drug raises serious problems, because the toxic doses of lithium are quite close to the therapeutic ones. Thus, precise characterization of the target(s) involved in the therapeutic activity of lithium is of importance. The present work, carried out at molecular, cellular, and in vivo levels, demonstrates that 5-HT1B receptor constitutes a molecular target for lithium. Several reasons suggest that this interaction is more likely related to the therapeutic properties of lithium than to its undesirable effects. First, the observed biochemical and functional interaction occurs at concentrations that precisely correspond to effective therapeutic doses of lithium. Second, 5-HT1B receptors are well characterized as controlling the activity of the serotonergic system, which is known to be involved in affective disorders and the mechanism of action of various antidepressants. These findings represent progress in our knowledge of the mechanism of action of lithium that may facilitate clinical use of the ion and also open new directions in the research of antidepressant therapies.
Massot
O
O
Unité de Pharmacologie Neuro-Immuno-Endocrinienne, Institut Pasteur, Paris, France.
Rousselle
J C
JC
Fillion
M P
MP
Januel
D
D
Plantefol
M
M
Fillion
G
G
D016475:3T3 Cells; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001667:Binding, Competitive; D001792:Blood Platelets / Q000378:metabolism; D016466:CHO Cells; D002412:Cations / Q000378:metabolism; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D008094:Lithium / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D019964:Mood Disorders / Q000188:drug therapy / Q000378:metabolism*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D013462:Sulfur Radioisotopes; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D000928:Antidepressive Agents; D002412:Cations; C470302:HTR1B protein, human; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013462:Sulfur Radioisotopes; D012701:Serotonin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D008094:Lithium