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

Abstract

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-HT_1C/ 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-HT_1C receptor agonist but a 5-HT₂ antagonist stimulated directly PI turnover, yet mCPP inhibited 5-HT-stimulated PI response. These findings indicate that both 5HT_1C 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-chlorophenylalanine (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.