Substance P selectively decreases paired pulse depression in the rat hippocampal slice

Background Although being widespread in the hippocampus, the role tachykinins play in synaptic transmission is unclear. The effect of substance P on field potentials evoked by stimulation of the Schaffer collateral-commissural fibres and recorded from the CA1 region of the rat hippocampal slice were studied. Results Perfusion of substance P (8 μM) had no effect on the fEPSP or population spike. Substance P did however cause a selective reduction in the paired pulse depression of population spikes evoked by paired stimulation at interpulse intervals of 20–80 msec. A comparison of the actions of other tachykinin receptor agonists gave an order of potency of substance P > [β-Ala8]-neurokinin A (4–10) > senktide. The effect of substance P was reduced by the neurokinin-1 receptor antagonist SR140333, but not by the neurokinin-2 or neurokinin-3 receptor antagonists, MDL 29,913 or [Trp7, β-Ala8]-neurokinin A (4–10). Conclusion The order of potency of the agonists, and the effects of the antagonists, both indicate that the effect of substance P on paired pulse depression is mediated by neurokinin-1 receptors.