Chronic lithium administration enhances serotonin release in the lateral hypothalamus but not in the hippocampus in rats. A microdialysis study.

Chronic administration of lithium displays therapeutic and prophylactic effects in bipolar affective disorders, but its mechanism of action remains unknown. Several studies in animals and humans strongly suggest that central serotonergic neurons might be involved in lithium effects. In the experiments reported here microdialysis with removable probes and high pressure liquid chromatography and electrochemical detection were used to assess the amphetamine-induced release of serotonin (5-HT) and the 5-hydroxy-indoleacetic acid (5-HIAA) levels in the perifornical hypothalamus (PFH) and hippocampus (HP) of freely moving rats before and after chronic lithium chloride administration (2 meq/kg, as intragastric daily injections for 14 days). The serum lithium levels were 0.66 +/- 0.08 meq/l. After lithium treatment, the amphetamine-induced 5-HT release was significantly enhanced in the PFH but not so in the HP. Basal levels of 5-HIAA in the control group decreased but remained unchanged in the lithium group in the PFH. No change of basal levels of 5-HIAA was observed in the HP. The effect of lithium on the PFH could be related to the improvement of the autonomic and cyclic symptoms of patients with manic depressive disorders undergoing lithium therapy.