The effects of substance P analogues on the scratching, biting and licking response induced by intrathecal injection of N-methyl-D-aspartate in mice.

1. Intrathecal (i.t.) administration of N-methyl-D-aspartate (NMDA) elicited a dose-dependent behavioural response consisting of licking, biting and scratching in mice. 2. Repeated i.t. injections of 0.4 nmol NMDA, at 5 min intervals, resulted in the rapid development of desensitization to this NMDA-induced behavioural phenomenon. 3. The NMDA-induced response was dose-dependently inhibited by the simultaneous injection of a selective NMDA-receptor antagonist, D-2-amino-5-phosphonovaleric acid. 4. The substance P (SP) analogues [D-Pro2, D-Trp7,9] SP and [D-Arg1, D-Trp7,9, Leu11] SP (spantide) inhibited NMDA-induced behavioural responses in a dose-dependent manner. However, [D-Phe7, D-His9] SP (6-11), a SP analogue selective for neurokinin1 (NK1) receptors, failed to inhibit NMDA-induced responses even at a dose of 4.0 nmol. 5. These results indicate that NMDA-induced behavioural responses are mainly mediated through NMDA receptors without affecting NK1 receptors in the spinal cord.