Behavioral Activation of Neurokinin-1 Agonists in Relation to Enzymatic Degradation in the Spinal Cord

□ Intrathecal (i.t.) injection of substance P (SP) induced reciprocal hindlimb scratching directed mainly toward the abdominal regions in mice. This behavior pattern appeared within the first minute after i.t. injection of SP. Similar behavioral effects were produced by i. t. injection of neurokinin (NK)-1 agonists, physaiaemin (Phy) and [Sar9, Met(02)11] SP (Sar-SP). The duration of scratching varied among NK-1 agonists; of the NK-1 agonists used, Phy had the most long-lasting duration of scratching in contrast to SP that had a short duration. The rank order of scratching duration was Phy > Sar-SP > SP. SP was rapidly degraded by the solubilized enzyme extracted from the mouse spinal cord as determined by HPLC. Decay of the scratching response to these NK-1 agonists was parallel with the rate of their degradation by the solubilized enzyme. These results suggest that a relatively long-lasting scratching behavior induced by Phy is mainly attributed to the stability against peptidases in the spinal cord.