Lithium long-term treatment--does it act via serotonin?

The mode of action of lithium salts used in the prophylaxis of affective disorders is still unknown. During the last decade, animal data have provided considerable evidence that chronic administration of lithium within a "therapeutic range" induces 5-HT agonistic effects in the brain. Among other possible reasons this may be due to increased synthesis of 5-HT. After presenting the main animal data in this area, some recent findings in lithium-treated patients are reviewed supporting the biochemical and neurophysiological results. Taking into account that, firstly, lithium possesses antiaggressive effects in animals and men, and secondly, that (auto-)aggression seems to be related to a low concentration of 5-HIAA in CSF, and thirdly, that a close relationship exists between depression and aggressive behavior, the proof of 5-HT agonistic effects in humans may enable us to formulate an integrative theory on the mode of action of lithium salts.