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.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D004347:Drug Interactions; D019204:GTP-Binding Proteins / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism
D011985:Receptors, Serotonin; D012701:Serotonin; D006160:Guanosine Triphosphate; D008094:Lithium; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases