Developmental switch in the hippocampal serotonin receptor linked to phosphoinositide hydrolysis

5-HT 2A and 5-HT 2C receptors couple to the phosphoinositide hydrolysis signal transduction pathway. The present pharmacological analyses provide evidence for a switch in the functional 5-HT receptor in rat hippocampus (from 5-HT 2A to 5-HT 2C) between the first and third weeks of life. Spiperone and MDL 100,507, antagonists that bind with 300- to 1000-fold higher affinity to 5-HT 2A receptors, blocked 5-HT-induced phosphoinositide hydrolysis in hippocampi of 7-day-old, but not 21-day-old, rats. In contrast, the non-selective 5-HT 2A/2C receptor antagonists, mesulergine and mianserin, blocked 5-HT-mediated phosphoinositide hydrolysis 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-HT 2A receptors, while in 21-day-old rats the phosphoinositide hydrolysis signal is mediated in large part by 5-HT 2C receptors. Neither 5-HT 2A or 5-HT 2C 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 that the hippocampal 5-HT receptor that links to phosphoinositide hydrolysis switches during postnatal development of rats, perhaps reflecting differences in the coupling of 5-HT 2A and 5-HT 2C receptors to intracellular effector molecules.