Nociceptin-induced scratching, biting and licking in mice: Involvement of spinal NK₁ receptors

1. Intrathecal (i.t.) injection of nociceptin at small doses (fmol order) elicited a behavioural response consisting of scratching, biting and licking in conscious mice. Here we have examined the involvement of substance P-containing neurons by using i.t. injection of tachykinin neurokinin (NK)₁ receptor antagonists and substance P (SP) antiserum. 2. Nociceptin-induced behavioural response was evoked significantly 5-10 min after i.t. injection and reached a maximum at 10-15 min. Dose-dependency of the induced response showed a bell-shaped pattern from 0.375-30.0 fmol, and the maximum effect was observed at 3.0 fmol. 3. The behavioural response elicited by nociceptin (3.0 fmol) was dose-dependently inhibited by intraperitoneal (i.p.) administration of morphine. 4. The NK₁ receptor antagonists, CP-96,345, CP-99,994 and sendide, inhibited nociceptin-induced behavioural response in a dose-dependent manner. A significant antagonistic effect of [D-Phe⁷, D-His⁹]SP (6-11), a selective antagonist for SP receptors, was observed against nociceptin-induced response. The NK₂ receptor antagonist, MEN-10376, had no effect on the response elicited by nociceptin. 5. Pretreatment with SP antiserum resulted in a significant reduction of the response to nociceptin. No significant reduction of nociceptin-induced response was detected in mice pretreated with NKA antiserum. 6. The N-methyl-D-aspartate (NMDA) receptor antagonists, dizocilpine (MK-801) and D(-)-2-amino5-phosphonovaleric acid (APV) (D-APV), and L-N(G)-nitro arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, failed to inhibit nociceptin-induced behavioural response. 7. The present results suggest that SP-containing neurons in the mouse spinal cord may be involved in elicitation of scratching, biting and licking behaviour following i.t. injection of nociceptin.