Activation of 5-HT1A receptors inhibits carbachol-stimulated inositol 1,4,5-trisphosphate mass accumulation in the rodent hippocampus.

We have previously demonstrated that 5-HT1A receptor agonists partially prevent the stimulation by carbachol of [3H]-phosphoinositide hydrolysis in immature rat hippocampal slices. This negative modulation has been investigated further by measuring, using a radioreceptor assay, the mass accumulation of IP3. In hippocampal slices from developing rats and in hippocampal neurons, carbachol enhanced the accumulation of IP3 and this response was partially inhibited by 8-OH-DPAT with a potency compatible with the affinity of this agonist for 5-HT1A receptors. The inhibition of the carbachol response by 8-OH-DPAT was non-competitive in nature and 8-OH-DPAT did not affect the inhibitory potency of pirenzepine. The inhibitory effect of 8-OH-DPAT was maintained after washing the slices preincubated with this compound but was not observed on the carbachol-stimulated PIP2 hydrolysis in hippocampal membranes, suggesting that this compound induces long lasting changes of muscarinic receptors and/or their effector mechanism by an indirect action.