Subchronic administration of para-chlorophenylalanine enhances serotonin-stimulated phosphoinositide hydrolysis in rat hippocampal slices.

Serotonin (5-HT) caused a dose-dependent accumulation of inositol monophosphate (IP-1) in rat hippocampal slices (maximal effect + 172%, EC50 = 630 nM) in the presence of LiCl. The 5-HT response was blocked potently by a non-selective 5-HT receptor antagonist metergoline and a 5-HT1C/5-HT2 receptor antagonist ritanserin. The 5-HT2 receptor antagonist ketanserin and spiperone were, however, less potent at inhibiting the 5-HT response. m-Chlorophenylpiperazine (mCPP), a 5-HT1C receptor agonist but a 5-HT2 antagonist stimulated directly PI turnover, yet mCPP inhibited 5-HT-stimulated PI response. These findings indicate that both 5-HT1C and 5-HT2 receptors are involved with a complicated interaction of each receptor in 5-HT-stimulated PI hydrolysis in rat hippocampus. 10-Day treatment with para-chlorophenyl-alanine (PCPA), a 5-HT synthesis inhibitor, resulted in a significant increase (maximal effect + 225%, EC50 = 580 nM) in 5-HT-stimulated IP-1 accumulation with no substantial change in EC50 value, which suggest that subchronic treatment with PCPA enhances the 5-HT-mediated PI hydrolysis in rat hippocampus.