The functional role of serotonin(7) receptors in rat hippocampal neurons: Glucocorticoid receptor regulation and therapeutic action of amitriptyline

Handling for the first week of life has been observed to increase glucocorticoid receptor (GR) levels selectively in the hippocampus and frontal cortex. The handling effect is specific to GR, mineralocorticoid receptor (MR) levels are not altered. Handling results in a high turnover of serotonin. In vitro, serotonin (5-hydroxytryptamine, 5-HT) treatment markedly increases cAMP formation and GR expression in hippocampal neurons. We wanted to explore the cellular mechanism involved in GR regulation. Primary hippocampal cell cultures treated with 5-carboxamidotryptamine (5-CT) or 5-HT for five days resulted in an increase in GR levels as measured by receptor binding and Western blotting. This effect was abolished by methiothepin and H8, a protein kinase A inhibitor, but not by pindolol. Cyclic AMP formation was enhanced with 5-CT treatment and was blocked by methiothepin and ritanserin, but not by pindolol. These results led us to examine the possibility of a 5-HT7 receptor mediating the effect of 5-HT on GR expression.; We also investigated the therapeutic action of amitriptyline on GR expression. (Abstract shortened by UMI.)...