Lithium decreases 5-HT1 receptors but increases 5-HT-sensitive adenylate cyclase activity in rat hippocampus

The effect of lithium (Li) treatment on serotonin1 (5-HT1) receptors and 5-HT-sensitive adenylate cyclase (ACase) activity in rat hippocampus was studied. [3H]5-HT binding to 5-HT1 receptors was decreased after either subacute (5 days) or chronic (3 weeks) treatment. In contrast, 5-HT-stimulated [3H]cyclic adenosine monophosphate ([3H]cAMP) formation was unchanged after 5 days of Li treatment, but was increased after 3 weeks of treatment. There was no difference in the inhibitory effects of guanosine triphosphate (GTP) on [3H]5-HT binding between the subacute Li and control groups. In addition, [3H]cAMP formation induced by GTP was not changed in the subacute group, whereas chronic treatment decreased it. These results suggested that chronic Li treatment caused the facilitation of 5-HT-sensitive ACase activity in spite of a decrease in the density of 5-HT1 receptors in the hippocampus. The enhancement of the coupling between receptor and ACase seemed not to be involved in these Li effects.