DEVELOPMENTAL SWITCH IN THE HIPPOCAMPAL SEROTONIN RECEPTOR-LINKED TO PHOSPHOINOSITIDE HYDROLYSIS

5-HT2A and 5-HT2C receptors couple to the phosphoinositide hydrolysis signal transduction pathway. The present pharmacological analyses prov ide evidence for a switch in the functional 5-HT receptor in rat hippo campus (from 5-HT2A to 5-HT2C) between the first and third weeks of li fe. Spiperone and MDL 100,507, antagonists that bind with 300- to 1000 -fold higher affinity to 5-HT2A receptors, blocked 5-HT-induced phosph oinositide hydrolysis in hippocampi of 7-day-old, but not 21-day-old, rats. In contrast, the non-selective 5-HT2A/2C receptor antagonists, m esulergine and mianserin, blocked 5-HT-mediated phosphoinositide hydro lysis in both 7- and 21-day-old rats. These results suggest that the 5 -HT-induced phosphoinositide hydrolysis signal in hippocampus of 7-day -old rats is mediated predominantly by 5-HT2A receptors, while in 21-d ay-old rats the phosphoinositide hydrolysis signal is mediated in larg e part by 5-HT2C receptors. Neither 5-HT2A or 5-HT2C receptor mRNA nor the binding site densities of the two receptors were altered between the two ages, ruling out developmental changes in receptor density as an explanation for the observed differences. We conclude therefore tha t the hippocampal 5-HT receptor that links to phosphoinositide hydroly sis switches during postnatal development of rats, perhaps reflecting differences in the coupling of 5-HT2A and 5-HT2C receptors to intracel lular effector molecules.